Guideline Number: NIA_CG_024 Last Review Date: January 2011 Responsible Department: Last Revised Date: May 2, 2011 Clinical Operations

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National Imaging Associates, Inc. Clinical guidelines NUCLEAR CARDIAC IMAGING (MYOCARDIAL PERFUSION STUDY) CPT Codes: 78451, 78452, 78453, 78454, 78466, 78468, 78469, 78481, 78483, 78494, 78499 Original Date: October 6, 2009 Page 1 of 11 FOR HIGHMARK MEMBERS ONLY Last Review Date: Guideline Number: NIA_CG_024 Last Review Date: January 2011 Responsible Department: Last Revised Date: May 2, 2011 Clinical Operations INTRODUCTION: FOR HIGHMARK MEMBERS ONLY Stress tests are done to assess cardiac function in terms of heart s ability to respond to increased work. Stress testing can be done without imaging including Standard Exercise Treadmill Testing (ETT) or with imaging including Stress Echocardiography (SE) and nuclear myocardial perfusion imaging (MPI). Exercise Treadmill Testing (ETT) is often an appropriate first line test in many patients with suspected CAD. However, there are patients in whom the test is not the best choice, for example those with resting ECG abnormalities, inability to exercise, and perimenopausal women. Stress Echocardiography is an initial imaging modality for the evaluation of coronary artery disease/ischemic heart disease when stress testing with imaging is indicated. It has similar sensitivity and superior specificity to MPI for evaluation of ischemic heart disease and avoids radiation. In addition to diagnostic capabilities stress echocardiography is useful in risk stratification and efficacy of therapy. Myocardial perfusion imaging is also often used as an initial test to evaluate the presence, and extent of coronary disease. Like stress echocardiography it is also used to risk stratify patients with and without significant disease. Similar to all stress testing MPI can be used for monitoring the efficacy of therapy and may have a more powerful role in the assessment of myocardial viability in patients who have had a myocardial infarction in whom interventions are contemplated. Perhaps it s most important distinction lies in the tests ability to obtain useful information in patients who are unable to exercise. In such cases drugs such as, dipyridamole, dobutamine, or adenosine, are administered to mimic the physiological effects of exercise. The common approach for stress testing by American College of Cardiology and American Heart Association indicates the following: Treadmill test: sensitivity 68%, specificity 77% Stress Echocardiogram: sensitivity 76%, specificity 88% Nuclear test: sensitivity 88%, specificity 77% ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 APPROPRIATE USE CRITERIA: 1 Nuc Card/MPI - Highmark Proprietary

ACCF et al. Criteria # MPI 2 INDICATIONS APPROPRIATE USE SCORE (4-9); (*Refer to Additional Information section) A= Appropriate; U=Uncertain Detection of CAD/Risk Assessment: Symptomatic Evaluation of Ischemic Equivalent (Non-Acute) Low pretest probability of CAD* ECG uninterpretable OR unable to exercise 3 Intermediate pretest probability of CAD* ECG interpretable AND able to exercise 4 5 14 Intermediate pretest probability of CAD* ECG uninterpretable OR unable to exercise High pretest probability of CAD* Regardless of ECG interpretability and ability to exercise A(9) A(8) Detection of CAD: Asymptomatic (Without Ischemic Equivalent) Asymptomatic Intermediate CHD risk (ATP III risk criteria)*** U(5) ECG uninterpretable 15 High CHD risk (ATP III risk criteria)*** A(8) 16 New-Onset or Newly Diagnosed Heart Failure With LV Systolic Dysfunction Without Ischemic Equivalent No prior CAD evaluation AND no planned coronary angiography A(8) New-Onset Atrial Fibrillation 17 Part of evaluation when etiology unclear U(6) Ventricular Tachycardia 18 Low CHD risk (ATP III risk criteria)*** 19 Intermediate or high CHD risk (ATP III risk criteria)*** A(8) Syncope 21 Intermediate or high CHD risk (ATP III risk criteria)*** Elevated Troponin 22 Troponin elevation without additional evidence of acute coronary syndrome Risk Assessment With Prior Test Results and/or Known Chronic Stable CAD Asymptomatic OR Stable Symptoms Normal Prior Stress Imaging Study 26 Intermediate to high CHD risk (ATP III risk criteria)*** Last stress imaging study done more than or equal to 2 U(6) 2 Nuc Card/MPI - Highmark Proprietary

ACCF et al. Criteria # MPI years ago INDICATIONS (*Refer to Additional Information section) APPROPRIATE USE SCORE (4-9); A= Appropriate; U=Uncertain Asymptomatic OR Stable Symptoms Abnormal Coronary Angiography OR Abnormal Prior Stress Imaging Study, No Prior Revascularization 28 Known CAD on coronary angiography OR prior abnormal stress imaging study Last stress imaging study done more than or equal to 2 years ago Prior Noninvasive Evaluation 29 Equivocal, borderline, or discordant stress testing where obstructive CAD remains a concern New or Worsening Symptoms 30 Abnormal coronary angiography OR abnormal prior stress imaging study 31 Normal coronary angiography OR normal prior stress imaging study Coronary Angiography (Invasive or Noninvasive) 32 Coronary stenosis or anatomic abnormality of uncertain significance Asymptomatic Prior Coronary Calcium Agatston Score 34 Low to intermediate CHD risk*** Agatston score between 100 and 400 35 High CHD risk*** Agatston score between 100 and 400 U(5) A(8) A(9) U(6) A(9) U(5) 36 Agatston score greater than 400 Duke Treadmill Score 38 Intermediate-risk Duke treadmill score**** 39 High-risk Duke treadmill score**** A(8) Risk Assessment: Preoperative Evaluation for Noncardiac Surgery Without Active Cardiac Conditions Intermediate-Risk Surgery 43 Greater than or equal to 1 clinical risk factor Poor or unknown functional capacity (less than 4 METs) Vascular Surgery 3 Nuc Card/MPI - Highmark Proprietary

ACCF et INDICATIONS al. Criteria # (*Refer to Additional Information section) MPI 47 Greater than or equal to 1 clinical risk factor Poor or unknown functional capacity (less than 4 METS) STEMI APPROPRIATE USE SCORE (4-9); A= Appropriate; U=Uncertain A(8) Risk Assessment: Within 3 Months of an Acute Coronary Syndrome 50 Hemodynamically stable, no recurrent chest pain A(8) symptoms or no signs of HF To evaluate for inducible ischemia No prior coronary angiography UA/NSTEMI 52 Minor perioperative risk predictor Normal exercise tolerance (greater than or equal to 4 METS) Hemodynamically stable, no recurrent chest pain symptoms or no signs of HF To evaluate for inducible ischemia No prior coronary angiography A(9) Risk Assessment: Postrevascularization (Percutaneous Coronary Intervention or Coronary Artery Bypass Graft) Symptomatic 55 Evaluation of ischemic equivalent A(8) Asymptomatic 56 Incomplete revascularization Additional revascularization feasible 57 Less than 5 years after CABG U(5) 58 Greater than or equal to 5 years after CABG 60 Greater than or equal to 2 years after PCI U(6) Assessment of Viability/Ischemia Ischemic Cardiomyopathy/Assessment of Viability 62 Known severe LV dysfunction Patient eligible for revascularization INDICATIONS FOR A NUCLEAR CARDIAC IMAGING/MYOCARDIAL PERFUSION STUDY: To qualify for SPECT MPI, the patient must meet ACCF/ASNC Appropriateness criteria for appropriate indications above. A(9) 4 Nuc Card/MPI - Highmark Proprietary

INDICATIONS THAT REQUIRE FURTHER CLINICAL REVIEW: Patients that meet ACCF/ASNC Inappropriate use score of (1-3) noted below OR meets any one of the following: o Heart transplant recipients OR o Follow-up to a previous Nuclear Cardiac Imaging (MPI) not meeting above indications ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 APPROPRIATE USE CRITERIA: # INDICATIONS (*Refer to Additional Information section) APPROPRIAT E USE SCORE (1-3); I= Inappropriate; Detection of CAD/Risk Assessment: Symptomatic 1 Evaluation of Ischemic Equivalent (Non-Acute) Low pretest probability of CAD* ECG interpretable OR able to exercise Acute Chest Pain 10 Definite ACS* I (1) Acute Chest Pain (Rest Imaging only) Detection of CAD: Asymptomatic (Without Ischemic Equivalent) Asymptomatic 12 Low CHD risk (ATP III risk criteria)*** I (1) 13 Intermediate CHD risk (ATP III risk criteria)*** ECG interpretable Syncope 20 Low CHD risk (ATP III risk criteria)*** Risk Assessment With Prior Test Results and/or Known Chronic Stable CAD Asymptomatic OR Stable Symptoms Normal Prior Stress Imaging Study 23 Low CHD risk (ATP III risk criteria)*** Last stress imaging study done less than 2 years ago 24 Intermediate to high CHD risk (ATP III risk criteria)*** Last stress imaging study done less than 2 years ago 25 Low CHD risk (ATP III risk criteria)*** Last stress imaging study done more than or equal to 2 years ago Asymptomatic OR Stable Symptoms Abnormal Coronary Angiography OR Abnormal Prior Stress Imaging Study, No Prior Revascularization 27 Known CAD on coronary angiography OR prior abnormal stress imaging study I (1) 5 Nuc Card/MPI - Highmark Proprietary

# INDICATIONS (*Refer to Additional Information section) Last stress imaging study done less than 2 years ago APPROPRIAT E USE SCORE (1-3); I= Inappropriate; Asymptomatic Prior Coronary Calcium Agatston Score 33 Agatston score less than 100 I (2) Duke Treadmill Score 37 Low-risk Duke treadmill score**** I (2) Risk Assessment: Preoperative Evaluation for Noncardiac Surgery Without Active Cardiac Conditions Low-Risk Surgery 40 Preoperative evaluation for noncardiac surgery risk assessment Intermediate-Risk Surgery 41 Moderate to good functional capacity (greater than or equal to 4 METs) 42 No clinical risk factors I (2) 44 Asymptomatic up to 1 year postnormal catherization, noninvasive test, or previous revascularization Vascular Surgery 45 Moderate to good functional capacity (greater than or equal to 4 METs) 46 No clinical risk factors I (2) I (1) I (2) 48 Asymptomatic up to 1 year postnormal catherization, noninvasive test, or previous revascularization I (2) STEMI Risk Assessment: Within 3 Months of an Acute Coronary Syndrome 49 Primary PCI with complete revascularization No recurrent symptoms 51 Hemodynamically unstable, signs of cardiogenic shock, or mechanical complications ACS Asymptomatic Postrevascularization (PCI or CABG) 53 Evaluation prior to hospital discharge I (1) Cardiac Rehabilitation I (2) I (1) 6 Nuc Card/MPI - Highmark Proprietary

# INDICATIONS (*Refer to Additional Information section) 54 Prior to initiation of cardiac rehabilitation (as a stand-alone indication) APPROPRIAT E USE SCORE (1-3); I= Inappropriate; Risk Assessment: Postrevascularization (Percutaneous Coronary Intervention or Coronary Artery Bypass Graft) Asymptomatic 59 Less than 2 years after PCI Cardiac Rehabilitation 61 Prior to initiation of cardiac rehabilitation (as a stand-alone indication) ADDITIONAL INFORMATION: Aortic valve dysfunction* Severe Aortic Stenosis (AS) is defined as o Jet velocity (m per second) - Greater than 4.0 o Mean gradient (mm Hg) - Greater than 40 o Valve area (cm2) - Less than 1.0 o Valve area index (cm2 per m2) - Less than 0.6 Severe Aortic Regurgitation (AR) is defined as o Qualitative Angiographic grade - 3 4 + Color Doppler jet width - Central jet, width greater than 65% LVOT Doppler vena contracta width (cm) - Greater than 0.6 o Quantitative (cath or echo) Regurgitant volume (ml per beat) - Greater than or equal to 60 Regurgitant fraction (%) - Greater than or equal to 50 Regurgitant orifice area (cm2) - Greater than or equal to 0.30 o Additional essential criteria Left Ventricular size Increased * Referred to ACC/AHA Practice guidelines for Classification of the Severity of Valve Disease in Adults. http://circ.ahajournals.org/cgi/reprint/114/5/e84 Electrocardiogram (ECG) Uninterpretable Refers to ECGs with resting ST-segment depression ( 0.10 mv), complete LBBB, preexcitation Wolff-Parkinson-White Syndrome (WPW), or paced rhythm. Acute Coronary Syndrome (ACS): 7 Nuc Card/MPI - Highmark Proprietary

Patients with an ACS include those whose clinical presentations cover the following range of diagnoses: unstable angina, myocardial infarction without ST-segment elevation (NSTEMI), and myocardial infarction with ST-segment elevation (STEMI) *Pretest Probability of CAD for Symptomatic (Ischemic Equivalent) Patients: Typical Angina (Definite): Defined as 1) substernal chest pain or discomfort that is 2) provoked by exertion or emotional stress and 3) relieved by rest and/or nitroglycerin. Atypical Angina (Probable): Chest pain or discomfort that lacks 1 of the characteristics of definite or typical angina. Nonanginal Chest Pain: Chest pain or discomfort that meets 1 or none of the typical angina characteristics. Once the presence of symptoms (Typical Angina/Atypical Angina/Non angina chest pain/asymptomatic) is determined, the probabilities of CAD can be calculated from the risk algorithms as follows: Age (Years) Gender Typical/Definite Angina Pectoris Atypical/Probable Angina Pectoris Nonanginal Chest Pain Asymptomatic <39 40 49 50 59 >60 o o o o Men Intermediate Intermediate Low Very low Women Intermediate Very low Very low Very low Men High Intermediate Intermedia Low te Women Intermediate Low Very low Very low Men High Intermediate Intermedia Low te Women Intermediate Intermediate Low Very low Men High Intermediate Intermedia Low te Women High Intermediate Intermedia Low te Very low: Less than 5% pretest probability of CAD Low: Less than 10% pretest probability of CAD Intermediate: Between 10% and 90% pretest probability of CAD High: Greater than 90% pretest probability of CAD **TIMI Risk Score: The TIMI risk score is determined by the sum of the presence of 7 variables at admission; 1 point is given for each of the following variables: age 65 years, at least 3 risk factors for CAD, prior coronary stenosis of 50%, ST-segment deviation on ECG presentation, at least 2 anginal events in prior 24 hours, use of aspirin in prior 7 days, and elevated serum cardiac biomarkers Low-Risk TIMI Score: TIMI score <2 High-Risk TIMI Score: TIMI score 2 8 Nuc Card/MPI - Highmark Proprietary

***Coronary Heart Disease (CHD) Risk (Based on the ACC/AHA Scientific Statement on Cardiovascular Risk Assessment): Absolute risk is defined as the probability of developing CHD, including myocardial infarction or CHD death over a given time period. The ATP III report specifies absolute risk for CHD over the next 10 years. CHD risk refers to 10-year risk for any hard cardiac event. CHD Risk Low Defined by the age-specific risk level that is below average. In general, low risk will correlate with a 10-year absolute CHD risk less than 10%. CHD Risk Moderate Defined by the age-specific risk level that is average or above average. In general, moderate risk will correlate with a 10-year absolute CHD risk between 10% and 20%. CHD Risk High Defined as the presence of diabetes mellitus in a patient 40 years of age or older, peripheral arterial disease or other coronary risk equivalents, or a 10-year absolute CHD risk of greater than 20%. **** Duke Treadmill Score The equation for calculating the Duke treadmill score (DTS) is, DTS = exercise time - (5 * ST deviation) - (4 * exercise angina), with 0 = none, 1 = non limiting, and 2 = exercise-limiting. The score typically ranges from -25 to +15. These values correspond to low-risk (with a score of >/= +5), intermediate risk (with scores ranging from - 10 to + 4), and high-risk (with a score of </= -11) categories. Perioperative Clinical Risk Factors: o History of ischemic heart disease o History of compensated or prior heart failure o History if cerebrovascular disease o Diabetes mellitus (requiring insulin) o Renal insufficiency (creatinine >2.0) 9 Nuc Card/MPI - Highmark Proprietary

APPLICABLE CPT/HCPCS CODES: 78451 Myocardial perfusion imaging, tomographic (SPECT) (including attenuation correction, qualitative or quantitative wall motion, ejection fraction by first pass or gated technique, additional quantification, when performed); single study, at rest or stress (exercise or pharmacologic) 78452 Myocardial perfusion imaging, tomographic (SPECT) (including attenuation correction, qualitative or quantitative wall motion, ejection fraction by first pass or gated technique, additional quantification, when performed); multiple studies, at rest and/or stress (exercise or pharmacologic) and/or redistribution and/or rest re injection 78453 Myocardial perfusion imaging, planar (including qualitative or quantitative wall motion, ejection fraction by first pass or gated technique, additional quantification, when performed); single study, at rest or stress (exercise or pharmacologic) 78454 Myocardial perfusion imaging, planar (including qualitative or quantitative wall motion, ejection fraction by first pass or gated technique, additional quantification, when performed); multiple studies, at rest and/or stress (exercise or pharmacologic) and/or redistribution and/or rest reinjection 78466 Myocardial imaging, infarct avid, planar; qualitative or quantitative 78468 Myocardial imaging, infarct avid, planar; with ejection fraction by first pass technique 78469 Myocardial imaging, infarct avid, planar; tomographic SPECT with or without quantification 78481 Cardiac blood pool imaging (planar), first pass technique; single study, at rest or with stress (exercise and/or pharmacologic), wall motion study plus ejection fraction, with or without quantification 78483 Cardiac blood pool imaging (planar), first pass technique; multiple studies, at rest and with stress (exercise and/or pharmacologic), wall motion study plus ejection fraction, with or without quantification 78494 Cardiac blood pool imaging, gated equilibrium, SPECT, at rest, wall motion study plus ejection fraction, with or without quantitative processing 78499 Unlisted cardiovascular procedure, diagnostic nuclear medicine 10 Nuc Card/MPI - Highmark Proprietary

REFERENCES ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM (2009) 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 Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine Endorsed by the American College of Emergency Physicians. J Am Coll Cardiol, 53, 2201-2229. doi:10.1016/j.jacc.2009.02.013 Baird, M.G., Bateman, T.M., Berman, D.S., et al. (2003, Oct 1). ACC/AHA/ASNC Guidelines for the Clinical Use of Cardiac Radionuclide Imaging. 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). Retrieved on November 18, 2010 from: http://www.americanheart.org/downloadable/heart/1061222494555rnifulltextfinal.pd f Berman, D.S., Hachamovitch, R., Shaw, L.J., Friedman, J.D., Hayes, S.W., Thomson, L.E.G., Rozanski, A. (2006). Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance: Noninvasive risk stratification and a conceptual framework for the selection of noninvasive imaging tests in patients with known or suspected coronary artery disease. Nucl Med, 47(7), 1107-1118. Dorbala, S., Hachamovitch, R., & DiCarli, M. (2006). Myocardial perfusion imaging and multidetector computed tomographic coronary angiography: Appropriate for all patients with suspected coronary artery disease? J Am Coll Cardiol, 48, 2515-2517. Ferd-Esfahani, A., Assadi, M., Saghari, M., Mohagheghie, A., Fallahi, B., Eftekhari, M., Ansari-Gilani, K. (2009). The role of myocardial perfusion imaging in the evaluation of patients undergoing percutaneous transluminal coronary angioplasty. Hellenic J Cardiol, 50, 396-401. Jeevanantham, V., Manne, K., Sengodhan, M., Haley, J.M., & Hsi, D.H. (2009). Predictors of coronary artery disease in patients with left bundle branch block who undergo myocardial perfusion imaging. Cardiology Journal, 16(4), 321-326. Klocke, F.J., Baird, M.G., Lorell, B.H., et al. (2003 September 16) 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, 108(11), 1404-1418. 11 Nuc Card/MPI - Highmark Proprietary