Coverage Policy Manual
Policy #: 1997167
Category: Radiology
Initiated: April 1996
Last Review: October 2024
  PET Scan, Positron Emission Tomography, for Cardiac Applications
Description:
Note: This policy is intended for those members with contracts that do not have requirements for prior approval for imaging procedures through an independent imaging review organization.
 
Positron emission tomography (PET) scans use positron-emitting radionuclide tracers, which simultaneously emit 2 high-energy photons in opposite directions. These photons can be simultaneously detected (referred to as coincidence detection) by a PET scanner, comprising multiple stationary detectors that encircle the thorax. Compared with single photon emission computed tomography (SPECT) scans, coincidence detection offers a greater spatial resolution. PET has been investigated as an option to diagnose and evaluate patients with cardiac conditions such as coronary artery disease, left ventricular dysfunction, and cardiac sarcoidosis.
 
Background
Heart disease is the leading cause of death for men and women in the United States (U.S.) (CDC, 2022). Heart disease is also the leading cause of death for people of most racial and ethnic groups in the U.S., including African American, American Indian, Alaska Native, Hispanic, and white men. For women from the Pacific Islands and Asian American, American Indian, Alaska Native, and Hispanic women, heart disease is second only to cancer. Coronary artery disease (CAD) is the most common type of heart disease in the U.S., affecting 20.1 million adults. Angina is the most common symptom of CAD. Risk factors for CAD include being overweight, physical inactivity, poor diet, and smoking. A family history of heart disease also increases the risk for CAD, especially in cases where there is a family history of early onset heart disease (i.e., age 50 or younger).
 
Positron emission tomography (PET) scans use positron-emitting radionuclide tracers, which simultaneously emit 2 high energy photons in opposite directions. These photons can be simultaneously detected (referred to as coincidence detection) by a PET scanner, consisting of multiple stationary detectors that encircle the thorax. Compared to single photon emission computed tomography (SPECT) scans, coincidence detection offers greater spatial resolution.
 
For myocardial perfusion studies, patient selection criteria for PET scans involve an individual assessment of the pretest probability of CAD, based both on patient symptoms and risk factors. Patients at low risk for CAD may be adequately evaluated with exercise electrocardiography. Patients at high risk for CAD typically will not benefit from non-invasive assessment of myocardial perfusion; a negative test will not alter disease probability sufficiently to avoid invasive angiography. Accordingly, myocardial perfusion imaging is potentially beneficial for patients at intermediate risk of CAD (variably defined as 25% to 75% or 10% to 90% disease prevalence probability) (BCBSA TEC, 1995). Risk can be estimated using the patient’s age, sex, and chest pain quality. Below is a summary of patient populations at intermediate risk for CAD (Diamond, 1980).
 
Intermediate-risk ranges used in different studies may differ from the range used here. These pretest probability risk groups are based on a TEC Assessment (1995) and take into account spectrum effect. The American College of Cardiology guidelines have defined low risk as less than 10%, intermediate risk as 10% to 90%, and high risk as greater than 90%.
 
Individuals at Intermediate Risk for CAD According to Chest Pain Quality
 
Typical Angina Chest pain with all of the following characteristics: 1) substernal chest discomfort with characteristic quality and duration, 2) provoked by exertion or emotional stress, and 3) relieved by rest or nitroglycerin
Men ages 30-39
Women ages 30-60
 
Atypical Angina Chest pain that lacks one of the characteristics of typical angina
Men ages 30-70
Women ages 50 years and older
 
Nonanginal Chest Pain Chest pain that meets one or none of the typical angina characteristics
Men ages 50 years and older
Women ages 60 years and older
 
Body habitus can limit SPECT; particularly moderate-to-severe obesity, which can attenuate tissue tracer leading to inaccurate images. In patients for whom body habitus is expected to lead to suboptimal SPECT scans, PET scanning is preferred.
 
Among patients with CAD, myocardial perfusion imaging can be used to quantify myocardial blood flow and myocardial flow reserve (MFR) (Waller, 2014). Quantitative assessment of myocardial perfusion is sensitive for detection of ischemic tissue within the myocardium and can allow for accurate determination of risk for cardiovascular events. These quantitative measurements can also be predictive of adverse cardiovascular outcomes. For example, the presence of an abnormally low MFR can identify patients at higher risk of cardiovascular death.
 
Myocardial perfusion studies with PET are also useful in the diagnosis of cardiac sarcoidosis (Akaike, 2018). Perfusion studies performed in patients with sarcoidosis and suspected cardiac involvement can detect presence of inflammation, fibrosis of the myocardial tissue, and function and involvement of the left and right ventricles.
 
Patients selected to undergo PET scanning for myocardial viability are typically those with severe left ventricular dysfunction who are being considered for revascularization. A PET scan may determine whether the left ventricular dysfunction is related to the viable or nonviable myocardium. Patients with viable myocardium may benefit from revascularization but those with nonviable myocardium will not. As an example, PET scanning is commonly performed in potential heart transplant candidates to rule out the presence of viable myocardium.
 
A variety of radionuclide tracers are used for PET scanning, including fluorine-18, rubidium-82, oxygen-15, nitrogen-13, and carbon-11. Most tracers have a short half-life and must be manufactured with an on-site cyclotron. Rubidium-82 is produced by a strontium-82/rubidium-82 generator. The half-life of fluorine-18 is long enough that it can be manufactured commercially at offsite locations and shipped to imaging centers. The radionuclides may be coupled to a variety of physiologically active molecules, including oxygen, water, and ammonia. Fluorine-18 is often coupled with fluorodeoxyglucose (FDG) as a means of detecting glucose metabolism, which in turn reflects the metabolic activity, and thus viability, of the target tissue. Tracers that target the mitochondrial complex are also being developed.
 
Regulatory Status
A number of PET platforms have been cleared by the U.S. Food and Drug Administration (FDA) through the 510(k) process since the Penn-PET scanner was approved in 1989. These systems are intended to aid in detecting, localizing, diagnosing, staging, and restaging of lesions, tumors, disease, and organ function for the evaluation of diseases and disorders such as, but not limited to, cardiovascular disease, neurologic disorders, and cancer. The images produced by the system can aid in radiotherapy treatment planning and interventional radiology procedures.
 
PET radiopharmaceuticals have been evaluated and approved by the FDA for use as diagnostic imaging agents. These radiopharmaceuticals are approved for specific conditions.
 
In December 2009, the FDA issued guidance for Current Good Manufacturing Practice (CGMP) for PET drug manufacturers (FDA, 2009), and in August 2011, FDA issued similar CGMP guidance for small businesses (FDA, 2011). An additional final guidance document issued in December 2012 required all PET drug manufacturers and compounders to operate under an approved new drug application (NDA) or abbreviated NDA, or investigational new drug application, by December 2015 (FDA, 2012).
 
To avoid interruption of the use of PET radiotracers already in use in clinical practice, before the issuance of specific guidance documents, the FDA made determinations of safety and effectiveness for certain uses of PET radiotracers. The following radiopharmaceuticals used with PET for cardiac-related indications were reviewed in this manner and subsequently had approved NDAs as summarized below.
 
Radiopharmaceuticals Approved for Use With Positron Emission Tomography for Cardiac Indications
 
    • Fluorine 18 fluorodeoxyglucose (F-18-FDG), manufactured by Various, (NDA 20306) was approved in 2000 for CAD and left ventricular dysfunction, when used with myocardial perfusion imaging, to identify left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function
    • Ammonia N 13, manufactured by Zevacor Pharma, (NDA 22119) was approved in 2000 for Imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing CAD
    • Rubidium 82 chloride, manufactured by Bracco Diagnostics, (NDA 19414) was approved in 1989 for Assessing regional myocardial perfusion in the diagnosis and localization of myocardial infarction
 
 
Coding Issues
A PET scan essentially involves 3 separate activities: 1) manufacture of the radiopharmaceutical, which may be manufactured on site or manufactured at a regional delivery center with delivery to the institution performing PET; 2) actual performance of the PET scan; and 3) interpretation of the results. The following CPT codes and HCPCS codes are available to code for PET scans:
 
CPT code:
 
This CPT code describes the use of FDG to evaluate myocardial viability:
 
78459: Myocardial imaging, positron emission tomography (PET) metabolic evaluation.
 
These 2 CPT codes describe the use of rubidium to evaluate myocardial perfusion:
 
78491: Myocardial imaging, PET, perfusion: single study at rest or stress
78492: multiple studies at rest and/or stress
 
When the radiopharmaceutical is provided by an outside distribution center, there may be an additional separate charge, or this charge may be passed through and included in the hospital bill. In addition, there will likely be an additional transportation charge for radiopharmaceuticals that are not manufactured on site.
 
HCPCS
Effective in 2006, there are HCPCS codes for FDG, rubidium and N-13 ammonia:
A9552: Fluorodeoxyglucose F-18 FDG, diagnostic, per study dose, up to 45 millicuries
A9555: Rubidium Rb-82, diagnostic, per study dose, up to 60 millicuries
A9526: Nitrogen N-13 ammonia, diagnostic, per study dose, up to 40 millicuries
 
Note: Oncologic applications and other miscellaneous applications of PET scanning are considered in separate policies.
Policy/
Coverage:
Effective May 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Cardiac PET scanning to assess myocardial perfusion and thus diagnose coronary artery disease meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes (may be considered medically necessary):
 
        • In individuals with indeterminate SPECT scan; OR
 
        • In individuals who meet the criteria for SPECT scan but have ONE of the following contraindications to performing SPECT:
 
            • Morbid obesity (BMI > 40 kg/m2)
            • Breast implant(s) in situ
            • Known pericardial or pleural effusion
            • Prior mastectomy
            • Chest wall deformity
 
Cardiac PET scanning to assess the myocardial viability in individuals with severe left ventricular dysfunction as a technique to determine candidacy for a revascularization procedure meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Cardiac PET scanning for the diagnosis of cardiac sarcoidosis in individuals who are unable to undergo magnetic resonance imaging (MRI) scanning meets member benefit certificate primary coverage criteria.  Examples of patients who are unable to undergo MRI include, but are not limited to, patients with pacemakers, automatic implanted cardioverter-defibrillators (AICDs), or other metal implants.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Any other use of cardiac PET scanning does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria, any other use of cardiac PET scanning not specifically listed as covered  is considered investigational and is not covered. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective, September 2012 to April 2024
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Cardiac PET scanning to assess myocardial perfusion and thus diagnose coronary artery disease in patients with indeterminate SPECT scan; or in patients who may be prone to artifact that could lead to an indeterminate test, such as severely obese (BMI>35 kg/m2) patients meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Cardiac PET scanning to assess the myocardial viability in patients with severe left ventricular dysfunction as a technique to determine candidacy for a revascularization procedure meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Cardiac PET scanning for the diagnosis of cardiac sarcoidosis in patients who are unable to undergo magnetic resonance imaging (MRI) scanning meets member benefit certificate primary coverage criteria.  Examples of patients who are unable to undergo MRI include, but are not limited to, patients with pacemakers, automatic implanted cardioverter-defibrillators (AICDs), or other metal implants.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Any other use of cardiac PET scanning does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria, any other use of cardiac PET scanning not specifically listed as covered  is considered investigational and is not covered. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective, April 2011
Cardiac PET scanning to assess myocardial perfusion and thus diagnose coronary artery disease in patients with indeterminate SPECT scan; or in patients who may be prone to artifact that could lead to an indeterminate test, such as severely obese (BMI>35 kg/m2) patients meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Cardiac PET scanning to assess the myocardial viability in patients with severe left ventricular dysfunction as a technique to determine candidacy for a revascularization procedure meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
Any other use of cardiac PET scanning does not meet Primary Coverage Criteria that there be scientific evidence of effectiveness.
 
For contracts without Primary Coverage Criteria, any other use of cardiac PET scanning not specifically listed as covered  is considered investigational and is not covered. Investigational services are an exclusion in the member benefit certificate.
 
EFFECTIVE, prior to April 2011
Positron Emission Tomography (PET) for Myocardial Perfusion Imaging meets primary coverage criteria for effectiveness and is covered if the PET Scan is performed to evaluate for myocardial ischemia in patients who may be prone to artifact that could lead to an indeterminate SPECT scan, such as severe obesity (BMI greater than 35 kg/m2).
 
PET for Myocardial Viability Imaging and PET as a means to clarify an inconclusive SPECT are not covered because of Primary Coverage Criteria that the intervention be cost-effective.
 
Any other use of cardiac PET scanning does not meet Primary Coverage Criteria that there be scientific evidence of effectiveness.
 
For contracts without Primary Coverage Criteria, any other use of cardiac PET scanning not specifically listed as covered  is considered investigational and is not covered. Investigational services are an exclusion in the member benefit certificate.
Rationale:
In 2003, the American College of Cardiology (ACC) and the American Heart Association (AHA) published updated guidelines for cardiac radionuclide imaging (Klocke, 2008). Cardiac applications of positron emission tomography (PET) scanning were included in these guidelines. The ACC/AHA guidelines categorize specific indications for PET scanning to Class I, Class IIa, Class IIb, or Class III. Class I is defined as conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective. Class IIa is defined as conditions for which there is conflicting evidence or a divergence of opinion but the weight of evidence/opinion is in favor of usefulness/efficacy. Class IIb is similar to Class II except that the usefulness/efficacy is less well established by evidence/opinion. The medically necessary indications for PET myocardial perfusion studies in this policy are consistent with Class I and Class IIa indications in the ACC guidelines.
 
Myocardial Viability
PET has perhaps been most thoroughly researched as a technique to assess myocardial viability to determine candidacy for a coronary revascularization procedure. For example, a patient with a severe stenosis identified by coronary angiography may not benefit from revascularization if the surrounding myocardium is non-viable. A fixed perfusion defect, as imaged on single photon emission computed tomography (SPECT) scanning or stress thallium echocardiography, may suggest nonviable myocardium. However, a PET scan may reveal metabolically active myocardium, suggesting areas of “hibernating” myocardium that would indeed benefit from revascularization. The most common PET technique for this application consists of N-13 ammonia as a perfusion tracer and fluorine-18 fluorodeoxyglucose (FDG) as a metabolic marker of glucose utilization. A pattern FDG uptake in areas of hypoperfusion (referred to as FDG/blood flow mismatch) suggests viable, but hibernating myocardium. The ultimate clinical validation of this diagnostic test is the percentage of patients who experience improvement in left ventricular dysfunction after revascularization of hibernating myocardium, as identified by PET scanning.
 
SPECT scanning may also be used to assess myocardial viability. While initial myocardial uptake of thallium-201 reflects myocardial perfusion, redistribution after prolonged periods can be used as a marker of myocardial viability. Initial protocols required redistribution imaging after 24 to 72 hours. While this technique was associated with a strong positive predictive value, there was a low negative predictive value; i.e., 40% of patients without redistribution nevertheless showed clinical improvement after revascularization. The negative predictive value has improved with the practice of thallium reinjection. Twenty-four to 72 hours after initial imaging, patients receive a reinjection of thallium and undergo redistribution imaging.
 
The ACC/AHA guidelines conclude that PET imaging “appears to have slightly better overall accuracy for predicting recovery of regional function after revascularization in patients with left ventricular (LV) dysfunction than single photon techniques (i.e., SPECT scans).” However, the ACC guidelines indicate that either PET or SPECT scans are Class I indications for predicting improvement in regional and global LV function and natural history after revascularization, and thus do not indicate a clear preference for either PET or SPECT scans in this situation.
 
Further supporting the equivalency of these 2 testing modalities, Siebelink and colleagues performed a prospective randomized study comparing management decisions and outcomes based on either PET imaging or SPECT imaging in 103 patients with chronic coronary artery disease and left ventricular dysfunction who were being evaluated for myocardial viability (Siebelink, 2001). Management decisions included drug therapy or revascularization with either angioplasty or coronary artery bypass grafting. This study is unique in that the diagnostic performance of the 2 studies was tied to the actual patient outcomes. No difference in patient management or cardiac event-free survival was demonstrated between management based on the 2 imaging techniques. The authors concluded that either technique could be used for management of patients considered for revascularization with suspicion of jeopardized myocardium.
 
Myocardial Perfusion
In a patient with symptoms suggestive of coronary artery disease (CAD), an important clinical decision point is to determine whether invasive coronary angiography is necessary. A variety of noninvasive imaging tests, including PET (using rubidium-82) and SPECT scans have been investigated as a means of identifying reversible perfusion defects, which may reflect coronary artery disease, and thus identify patients appropriately referred for angiography. The following table summarizes the ACC guidelines for myocardial reperfusion for both SPECT and PET scans in patients with an intermediate risk of coronary artery disease (Siebelink, 2001).
 
Indication
 
1.) Identify extent, severity, and location (SPECT protocols vary according to whether patient can exercise
 
SPECT Class I
PET Class IIA
 
2.) Repeat test after 3-5 yrs after revascularization in selected high-risk asymptomatic patients (SPECT protocols vary according to whether patients can exercise)
 
SPECT Class IIa
 
3.) As initial test in patients who are considered to be at high risk (i.e. patients with diabetes or those with a more than 20% 10-year risk of a coronary disease event) (SPECT protocols vary according to whether patients can exercise)
 
SPECT Class IIa
 
4.) Myocardial perfusion PET when prior SPECT study has been found to be equivocal for diagnostic or risk stratification purposes.
 
SPECT Class N/A
PET Class I
 
The sensitivity and specificity of PET may be slightly better than SPECT. However, their diagnostic utilities are similar in terms of altering disease risk in a manner affecting subsequent decision making among patients with intermediate pretest probability of CAD. For example, a patient with a 50% pretest probability of CAD would have a 9% post-test probability of CAD following a negative PET scan compared to 13% after a negative SPECT. In either case, further testing would not likely be pursued.
 
Another consideration is that there are fewer indeterminate results with PET than SPECT. A retrospective study by Bateman et al (2006), matched 112 SPECT and 112 PET studies by gender, body mass index, and presence and extent of CAD and were compared for diagnostic accuracy and degree of interpretative certainty (age 65 years; 52% male; mean BMI=32 kg/m2; 76% with CAD diagnosed on angiography). Eighteen of 112 (16%) SPECT studies were classified as indeterminate compared to 4 of 112 (4%) PET studies. Liver and bowel uptake were believed to affect 6 of 112 (5%) PET studies, compared to 46 of 112 (41%) SPECT studies. In obese patients (BMI>30), the accuracy of SPECT was 67% versus 85% for PET; accuracy in nonobese patients was reported to be 70% for SPECT and 87% for PET (Beanlands, 2007).  Therefore, for patients with intermediate pretest probability of coronary artery disease, one should start with SPECT testing and only proceed to PET in indeterminate cases. In addition, since obese patients are more prone to liver and bowel artifact, PET testing is advantageous over SPECT in severely obese patients.
 
In 2005, a joint statement from the Canadian Cardiovascular Society, Canadian Association of Radiologists, Canadian Association of Nuclear Medicine, Canadian Nuclear Cardiology Society, Canadian Society of Cardiac Magnetic Resonance recommends (Class I recommendation, level B evidence) PET scanning for patients with intermediate pretest probability of CAD who have nondiagnostic noninvasive imaging tests or where such a test does not agree with clinical diagnosis, or may be prone to artifact that could lead to an equivocal other test, such as obese patients (Beanlands, 2007).
 
2006 Update
A literature review was conducted in May 2006. No clinical trials or studies were found that would alter the policy statements or policy guidelines noted above. Studies continued to show the equivalence of SPECT and PET. As one example, Slart and colleagues (Slart, 2005) concluded that there was overall good agreement between SPECT and PET for the assessment of myocardial viability in patients with severe left ventricular dysfunction. Comparative studies reported on test accuracy and did not address impact on clinical outcomes.
 
2007–2008 Update
The policy was updated with a literature review using MEDLINE in January 2008. While comparative studies were identified for SPECT compared to PET in the evaluation of coronary artery disease, the comparative data are still limited. Using a thorax-cardiac phantom, Knesaurek and Machac concluded that PET was better at detecting smaller defects (Knesaurek, 2006). In this study, a 1-cm insert was not detectable by SPECT yet it was detectable using PET. Merhige and colleagues reported on outcomes of non-contemporaneous patients with similar probabilities of coronary artery disease that were evaluated by SPECT or PET (Merhige, 2007).  In this study involving PET scans done at one center compared to those evaluated by SPECT, those receiving PET evaluations had lower rates of angiography (13% vs. 31%) and revascularization (6% and 11%) with similar rates of death and myocardial infarction at 1 year of follow-up. These results are viewed as preliminary and additional comparative studies showing impact on outcomes are needed. Another publication also described the PAREPET study that will determine whether the amount of viable dysfunctional myocardium and/or sympathetic dysinnervation is associated with the risk of sudden cardiac death (Fallavolita, 2006).
 
2009 Update
A literature review was conducted in September 2008. None of the articles identified would prompt a change in the policy statements above. A recent review by Di Carli and Hachamovitch (Di Carli, 2007) describes the current and potential diagnostic uses of cardiac PET and is in agreement with the policy statements. The Study of Perfusion and Anatomy’s Role in CAD (SPARC) trial is recruiting patients to evaluate the role of cardiac PET/CT for the diagnosis of coronary artery disease. To date, there are no articles from the PAREPET or SPARC trials. The policy statement is unchanged.
 
 2012 Update
 
Cardiac Sarcoidosis
Published evidence on the utility of PET scanning for cardiac sarcoidosis is limited due to the relatively small numbers of patients with this condition. A 2009 review article concluded that imaging studies had incremental value when combined with clinical evaluation and/or myocardial biopsy in the diagnosis of cardiac sarcoidosis (Sharma, 2009). This review reported that cardiac magnetic resonance imaging (MRI) was the more established imaging modality in diagnosing sarcoidosis, with an estimated sensitivity of 100% and specificity of 80%. There is limited evidence to define the sensitivity, specificity or predictive value of PET scanning for this purpose, but it appears to have reasonably good accuracy based on small series of patients.
 
Expert opinion offered that MRI scanning was the preferred test in the workup of cardiac sarcoidosis but that PET scanning was medically necessary in patients who were unable to undergo MRI. As a result of this input, an additional indication was added to the policy statement for workup of cardiac sarcoidosis:
 
Practice Guidelines and Position Statements
2011 Appropriateness Criteria from the American College of Radiology (ACR) considers both SPECT and PET to be appropriate for the evaluation of patients with a high probability of coronary artery disease (Earls, 2011). ACR states that PET perfusion imaging has advantages over SPECT, including higher spatial and temporal resolution. Routine performance of both PET and SPECT are not necessary.
 
Summary
Evidence from the medical literature supports the use of PET scanning to assess myocardial viability in patients with severe LV dysfunction who are being considered for revascularization. Results of primary studies and recommendations from specialty societies conclude that PET scanning is at least as good as, and likely superior, to SPECT scanning for this purpose. For assessing myocardial perfusion in patients with suspected coronary artery disease, PET scanning is less likely than SPECT scanning to provide indeterminate results. Therefore, PET scanning is also useful in patients with an indeterminate SPECT scan. It is also useful in patients whose body habitus is likely to result in indeterminate SPECT scans, for example patients with moderate to severe obesity. For patients who are undergoing a workup for cardiac sarcoidosis, MRI is the preferred initial test. However, for patients who are unable to undergo MRI, such as patients with a metal implant, based on expert opinion, PET scanning is the preferred test.
 
2013 Update
This policy was reviewed with a literature search using the MEDLINE database through August 2013 did not reveal any new literature that would prompt a change in the coverage statement.
 
A 2012 meta-analysis by Parker et al. compared SPECT and PET stress myocardial perfusion imaging, using coronary angiography as the reference standard (Parker, 2012). A total of 117 articles met selection criteria. SPECT was addressed by 113 studies (11,212 patients), while PET was examined in 9 studies (650 patients). Patient-level diagnostic accuracy data were pooled in a bivariate meta-analysis, showing significantly better sensitivity for PET (92.6%) compared with SPECT (88.3%). There was no significant difference in specificity between PET (81.3%) and SPECT (76.0%). The pattern of higher sensitivity for PET over SPECT and similar specificity was also found among higher quality studies.
 
A meta-analysis on the use of PET in the diagnosisi of cardiac sarcoidosis was published in 2012 (Youssef, 2012).  Youssef et al. identified 7 studies with 164 patients. Studies were selected if they used fluorodeoxyglucose (FDG) PET for diagnosis of cardiac sarcoidosis and used the criteria of the Ministry of Health, Labor and Welfare (MHLW) of Japan as the reference standard. Pooled sensitivity of PET by random effects meta-analysis was 89% and pooled specificity was 78%. Area under the summary receiver operating characteristic curve was 93%, suggesting a good level of diagnostic discrimination.
 
2014 Update
A literature search conducted using the MEDLINE database through August 2014 did not reveal any new information that would prompt a change in the coverage statement. Two ongoing randomized clinical trials were identified with a search of ClinicalTrials.gov.
 
An ongoing randomized controlled trial of cardiac imaging in ischemic heart failure (NCT01288560) with an estimated enrollment of 1261 is expected to be completed in March 2016. It includes patients with CAD and heart failure with a left ventricular ejection fraction of 45% or less. Patients are randomized to management algorithms guided either by SPECT or PET/MRI.
 
The ongoing, single-blind (assessor) CENTURY trial is a randomized lifestyle modification study for management of stable coronary artery disease (NCT00756379). A PET perfusion imaging-guided intensive lifestyle modification program will be compared with standard medical management. Although all patients will undergo PET perfusion imaging at baseline and at intervals throughout the trial, PET results for patients in the standard treatment arm will be blinded until the end of the study.
  
2015 Update
A literature search conducted through July 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Takx and colleagues reported a meta-analysis of studies that compared noninvasive myocardial perfusion imaging modalities (MRI, CT, PET, SPECT, and echocardiography) with coronary angiography plus fractional flow reserve (FFR) (Takx, 2014).  Literature was searched to May 2014, and 37 studies met inclusion criteria (4698 vessels). Three PET studies of moderate to high quality were included (870 vessels); pre-test probability of CAD was intermediate to intermediate-high in these studies. Negative likelihood ratio (NLR) was chosen as the primary outcome of interest because ruling out hemodynamically significant CAD is a primary purpose of noninvasive imaging. At the vessel level, pooled NLRs for PET, MRI, and CT were similar and were lower (better) than the pooled NLR for SPECT (PET pooled NLR: 0.15 [95% CI: 0.05 to 0.44]; SPECT pooled NLR: 0.47 [95% CI: 0.37 to 0.59]). Similarly, at the patient level, pooled NLRs for PET, MRI, and CT were better than the pooled NLRs for SPECT and echocardiography (PET pooled NLR: 0.14 [95% CI: 0.02 to 0.87]; SPECT pooled NLR: 0.39 [95% CI: 0.27 to 0.55]). Area under the receiver operating characteristic (AUC) analyses was similar at both the vessel level (PET: 0.95 vs SPECT: 0.83) and the patient level (PET: 0.93 vs SPECT: 0.82).
 
Quantified Myocardial Blood Flow
Stuijfzand and colleagues  used 15-O[H2O] PET imaging in 92 patients with 1-2 vessel disease to quantify myocardial blood flow, myocardial flow reserve (MFR, defined as stress myocardial blood flow/rest myocardial blood flow), and “relative flow reserve” (defined as stress myocardial blood flow in a stenotic area/stress myocardial blood flow in a normal perfused area) (Stuifzand, 2015).  Relative flow reserve was evaluated as a potential noninvasive alternative to FFR on coronary angiography. Using optimized cut points for PET detection of hemodynamically significant CAD (FFR as reference standard), AUC analysis showed similar diagnostic performance for all 3 measures (0.76 [95% CI: 0.66 to 0.86] for myocardial blood flow; 0.72 for MFR [95% CI: 0.61 to 0.83]; and 0.82 [95% CI: 0.72 to 0.91] for relative flow reserve; p>0.05 for all comparisons).
 
Taqueti and colleagues evaluated the association between MFR (termed “coronary flow reserve” in this study) and cardiovascular outcomes in 329 consecutive patients referred for invasive coronary angiography after stress PET perfusion imaging (Taqueti, 2015).  Patients with a prior history or coronary artery bypass grafting (CABG) or heart failure, or with left ventricular ejection fraction (LVEF) less that 40%, were excluded. Patients underwent rubidium-82 (Rb-82) or N-13 ammonia PET imaging and selective coronary angiography. MFR was calculated as the ratio of stress to rest myocardial blood flow for the whole left ventricle. The primary outcome was a composite of cardiovascular death and hospitalization for heart failure. These outcomes were chosen because they are thought to be related to microvascular dysfunction, which impacts PET myocardial blood flow measures, as opposed to obstructive CAD, which characteristically presents with myocardial infarction and/or revascularization. Patients were followed for a median of 3.1 years (interquartile range, 1.7–4.3) for the occurrence of major adverse cardiovascular events (MACE, comprising death, cardiovascular death, and hospitalization for heart failure or myocardial infarction). During follow-up, 64 patients (19%) met the primary composite end point. In a multivariate model that included pretest clinical score (to determine the pretest probability of obstructive, angiographic CAD), LVEF, left ventricular ischemia, early revascularization (within 90 days of PET imaging), and CAD prognostic index (CADPI), MFR was statistically associated with the primary outcome (hazard ratio [HR] per 1 unit decrease in continuous MFR score: 2.02 [95% CI: 1.20 to 3.40]). Using binary classification defined by median MFR, incidence of the primary outcome was 50% in patients with low or high CFR. A statistically significant interaction between CFR and early revascularization by CABG was observed: Event-free survival for patients with high CFR who underwent early revascularization was similar in groups who received CABG (n=17) or percutaneous coronary intervention (PCI; n=72) or no revascularization (n=79); among patients with low CFR who underwent early revascularization, event-free survival was significantly better in the CABG group (n=22) compared with the PCI group (n=85; adjusted log-rank test, p=0.006) and the no-revascularization group (n=57; adjusted log-rank test, p=0.001).
 
Evidence for the association of quantitative myocardial blood flow and myocardial flow reserve with cardiovascular outcomes is growing. Some but not all prospective studies have shown improvements over prognostic models based on clinical risk factors for cardiac events. Editorialists have commented on the potential utility of quantitative perfusion for understanding cardiac physiology and for informing future research (Gould, 2015a; Gould, 2015b). However, because some studies used data-driven cut points and did not include healthy volunteers to verify discriminative ability (spectrum bias), these methods are considered to be in a developmental stage for clinical use.
 
Yokoyama and colleagues reported an AUC of 0.96 for identifying patients with cardiac sarcoidosis using optimized cut points for the maximum standardized uptake value on FDG PET/CT (Yokoyama, 2015)
 
 
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this policy are listed below:
 
(NCT01288560) Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) Project I-A of Imaging  Modalities to Assist With Guiding Therapy and the Evaluation of Patients With Heart Failure (IMAGE-HF); planned enrollment 1511; projected completion date June 2017.
 
(NCT00756379) Randomized Trial of Comprehensive Lifestyle Modifications, Optimal Pharmacological Treatment and PET Imaging for Detection and Management of Stable Coronary Artery Disease; planned enrollment 1300; projected completion date January 2019.
 
(NCT01943903) Prospective Longitudinal Trial of FFRct: Outcome and Resource Impacts; planned enrollment 580; projected completion date December 2015.
 
(NCT01934985) Dynamic Cardiac SPECT Imaging; planned enrollment 160; projected completion date September 2015.
 
Studies of quantitative myocardial blood flow and myocardial flow reserve in patients with CAD indicates that these methods are in a developmental stage for clinical use. Current evidence is insufficient to permit conclusions about the impact on net health outcome in these patients.
 
2017 Update
 
A literature search conducted using the Medline database through August 2017. The key identified literature is summarized below.
 
Suspected Coronary Artery Disease
In 2016, Dai et al conducted a meta-analysis comparing the abilities of the following cardiac imaging modalities in diagnosing CAD: SPECT, PET, dobutamine stress echocardiography, cardiac MRI, and computed tomography (CT) perfusion imaging (Dai, 2016). The reference standard was FFR derived from CT. The literature search, conducted through June 2015, identified 74 studies for inclusion, 5 of which used PET. Study quality was assessed using Standards for Reporting Diagnostic Accuracy and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tools. Pooled sensitivity and specificity for PET were 90% (95% confidence interval [CI], 80% to 95%) and 84% (95% CI, 81% to 90%). These rates were similar to FFR, the reference standard (sensitivity, 90% [95% CI, 85% to 93%]; specificity, 75% [95% CI, 62% to 85%]).
 
In 2017, Chen et al published a meta-analysis assessing the prognostic value of PET myocardial perfusion imaging in patients with known or suspected CAD (Chen, 2017). For inclusion, studies had to have at least one of the following outcomes: mortality, cardiac infarction, or major adverse cardiac event (MACE). The literature search, conducted through June 2016, identified 11 studies for inclusion. Quality assessment was based on: (1) cohort follow-up of 90% or more; (2) blinded outcome assessors; and (3) corroboration of outcomes with hospital records or death certificates. Nine of the studies were of good quality, and two were fair. All 11 studies included cardiac death as the primary or secondary outcome, with a pooled negative predictive value (NPV) of 99% (95% CI, 98% to 99%). Seven studies included all-cause death as an outcome, with a pooled NPV of 95% (95% CI, 93% to 96%). Four studies included MACE as an outcome, with a pooled NPV of 90% (95% CI, 78% to 96%).
 
In 2017, Smulders et al published a meta-analysis comparing the prognostic value of the following negative noninvasive cardiac tests: coronary computed tomography angiography, cardiovascular MRI, exercise electrocardiographic testing, PET, stress echocardiography, and SPECT (Smulders, 2017). Outcomes of interest were annual event rates of myocardial infarction and cardiac death. The literature search, conducted through April 2015, identified 165 studies for inclusion, four of which involved PET. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies. Pooled annual event rates for cardiac death and myocardial infarction for PET were low (0.41; 95% CI, 0.15 to 0.80), indicating that a patient with a negative PET test has a good prognosis.
 
Severe LV Dysfunction Considering Revascularization
In 2016, Mc Ardle et al published long-term follow-up results for PARR-2 (McArdle, 2016). Six of the 9 original sites participated in the long-term follow-up study (197 patients in the PET-assisted arm, 195 patients in the standard care arm). Long-term results were similar to the 1-year results. The HR for time to composite event for the whole study population did not differ significantly between the PET-assisted group and the standard care group (0.82; 95% CI, 0.62 to 1.1); however, when analysis was conducted using only the subgroup of patients who adhered to the PET imaging-based recommendations, the HR was statistically significant (0.73; 95% CI, 0.54 to 0.99).
 
Siebelink et al (2001) performed a prospective randomized study comparing management decisions with outcomes based on PET imaging (n=49) or SPECT imaging (n=54) in patients who had chronic CAD and LV dysfunction and were being evaluated for myocardial viability (Siebelink, 2001). Management decisions based on readings of the PET or SPECT images included either drug therapy for patients without viable myocardium or revascularization with either angioplasty or coronary artery bypass grafting (CABG) for patients with viable myocardium. This study is unique in that diagnostic performance of PET and SPECT was tied to actual patient outcomes. No difference in patient management or cardiac event-free survival was demonstrated between management based on the 2 imaging techniques. The authors concluded that either technique could be used to manage patients considered for revascularization.
 
Cardiac Sarcoidosis
A 2012 meta-analysis by Youssef et al identified 7 studies (total N=164 patients) (Youssef, 2012). Studies were selected if they used FDG-PET for diagnosis of cardiac sarcoidosis and used criteria of the  japanese Ministry of Health, Labor and Welfare as the reference standard. The pooled sensitivity of PET by random-effects meta-analysis was 89%, and pooled specificity was 78%. The summary AUROC was 93%, suggesting a good level of diagnostic discrimination.
 
In 2017, Dweck et al published a study evaluating the usefulness of a hybrid of cardiac MRI and FDG-PET to diagnose cardiac sarcoidosis (Dweck, 2017). Patients with suspected cardiac sarcoidosis (N=25) underwent FDG-PET imaging simultaneously with cardiac MRI. The investigators categorized 4 patient groups (MRI+/PET+, MRI+/PET-, MRI-/PET+, MRI-/PET-). The patients with MRI+/PET+ results had increased FDG activity that corresponded with the pattern of injury indicating active cardiac sarcoidosis. The remaining patients, with MRI+/PET-, MRI-/PET+, and MRI-/PET- results, did not show evidence of active cardiac sarcoidosis. Detecting active cardiac sarcoidosis, which is frequently subclinical, is beneficial so that anti-inflammatory therapy can be initiated. The authors concluded that simultaneous assessment of MRI and disease activity with PET permits a more accurate assessment of pattern of injury and disease activity in a single scan, which can impact therapeutic management.
 
Yokoyama et al (2015) conducted a study on 92 consecutive patients with suspected cardiac sarcoidosis. The patients underwent FDG-PET/CT following clinical assessment and imaging (electrocardiogram, echocardiography, MRI, perfusion scintigraphy) at the discretion of their physicians. The authors reported an AUC of 0.96 for identifying patients with cardiac sarcoidosis using optimized cut points for the maximum standardized uptake value on FDG-PET/CT (Yokoyama, 2015).
 
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2018. No new literature was identified that would prompt a change in the coverage statement.
 
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2018. No new literature was identified that would prompt a change in the coverage statement. The key literature is summarized below.
 
Knuuti et al reported on the results of a meta-analysis of the performance of noninvasive tests to rule-in and rule-out significant coronary artery stenosis in patients with stable angina including publications through April 2017 that included at least 100 patients with stable CAD and either invasive coronary angiography (ICA) or ICA with fractional flow reserve (FFR) measurement as reference standard (Knuuti, 2018). A total of 132 studies (28,664 patients) using ICA as the reference standard and 23 studies (4131 patients) using FFR as the reference standard were included. The pooled analysis for the outcome of anatomically significant CAD included 418 patients for PET and the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were as follows: 90% (95% confidence interval [CI], 78% to 96%); 85% (95% CI, 78% to 90%); 5.87 (95% CI, 3.40 to 10.15); and 0.12 (95% CI, 0.05 to 0.29), respectively. The pooled analysis for outcome of functionally significant CAD included 709 patients for PET and the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio (NLR) were as follows: 89% (95% CI, 82% to 93%); 85% (95% CI, 81% to 88%); 6.04 (95% CI, 4.29 to 8.51); and 0.13 (95% CI, 0.08 to 0.22).
 
Juarez-Orozco et al reported on the results of a systematic review of prognostic studies of quantitative myocardial perfusion evaluation with PET (Juarez-Orozco, 2017). Eight studies (total N=6804 patients) were included (Herzog, 2009; Tio, 2009; Ziadi, 2011;Fukushima, 2011; Slart, 2011; Farhad, 2013; Maaniitty, 2017; Gupta, 2017). Risk of bias was assessed using the Quality in Prognostic Studies tool. The risk of bias was rated as low overall with the exception of 1 domain (prognostic factor measurement) with the uncertain risk of bias due to the differences in population characteristics and tracer used. The mean follow-up range was 12 to 117 months for the MACE outcome, 66 to 88 months for the cardiac death outcome, and 43 to 117 months for the all-cause mortality outcome. MFR was independently associated with MACE in all 8 studies with the range of adjusted HRs from 1.19 to 2.93. Pooled analyses for MACE included only 2 studies due to the differences in populations and cutoff values for MFR. There was not enough evidence to establish the prognostic value of MFR for cardiac death or all-cause mortality.
 
2020 Update
A literature search was conducted through January 2020.  There was no new information identified that would prompt a change in the coverage statement.  
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2021. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
American Thoracic Society
The American Thoracic Society published guideline recommendations on detection and diagnosis of sarcoidosis (ATS, 2020). This guideline generally recommends cardiac MRI over PET or transthoracic echocardiography (TTE) for obtaining diagnostic or prognostic information in patients with sarcoidosis and potential cardiac involvement. In cases where cardiac MRI is unavailable or inconclusive, PET is recommended over TTE to obtain diagnostic or prognostic information. Both of these recommendations are conditional and based on very low-quality evidence.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2022. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Xu et al conducted a meta-analysis that compared cardiac magnetic resonance imaging (MRI), SPECT, and PET for the diagnosis of CAD (Xu, 2021). Diagnostic studies were eligible for inclusion if either coronary angiography or fractional flow reserve (FFR) was used as the reference standard. The literature search, conducted through July 2020, identified 203 articles (N=23,942) that assessed the diagnostic performance of cardiac MRI (56 articles), SPECT (134 articles), and PET (25 articles). There were no statistically significant differences in sensitivities between cardiac MRI, SPECT, and PET (86% [95% CI, 84% to 88%], 83% [95% CI, 81% to 85%], 85% [95% CI, 80% to 89%], respectively; p=.109). For specificity, cardiac MRI (83% [95% CI, 81% to 86%]) and PET (86% [95% CI, 81% to 89%]) performed significantly better than SPECT (77% [95% CI, 74% to 80%]; p<.01 for both comparisons); there was no statistically significant difference between cardiac MRI and PET. Similarly, the area under the curve values of cardiac MRI (0.92 [95% CI, 0.89 to 0.94]), SPECT (0.87 [95% CI, 0.84 to 0.90]), and PET (0.92 [95% CI, 0.89 to 0.94) indicated that cardiac MRI and PET had better diagnostic performance for the detection of CAD as compared with SPECT (p<.01 for both comparisons).
 
Takx et al reported a meta-analysis of studies that compared noninvasive myocardial perfusion imaging modalities (MRI, CT, PET, SPECT, echocardiography) with coronary angiography plus FFR (Takx, 2015). Literature was searched to May 2014, and 37 studies met inclusion criteria ( N=4698 vessels). Three PET studies of moderate-to-high quality were included (870 vessels); pretest probability of CAD was intermediate to intermediate-high in these studies. Negative likelihood ratio was chosen as the primary outcome of interest because ruling out hemodynamically significant CAD is a primary purpose of noninvasive imaging. At the vessel level, pooled negative likelihood ratios for PET, MRI, and CT were similar and were lower (better) than the pooled negative likelihood ratio for SPECT (PET pooled negative likelihood ratio =0.15 [95% CI, 0.05 to 0.44]; SPECT pooled negative likelihood ratio =0.47 [95% CI, 0.37 to 0.59]). Similarly, at the patient-level, pooled negative likelihood ratios for PET, MRI, and CT were better than the pooled negative likelihood ratios for SPECT and echocardiography (PET pooled negative likelihood ratio =0.14 [95% CI, 0.02 to 0.87]; SPECT pooled negative likelihood ratio =0.39 [95% CI, 0.27 to 0.55]). The area under the receiver operating characteristic analyses was similar at both the vessel level (PET, 0.95 vs SPECT, 0.83) and the patient-level (PET, 0.93 vs SPECT, 0.82).
 
Several publications have described the use of PET imaging to quantify both MBF and MFR (Herzog, 2009; Schindler, 2010). However, as noted in an accompanying editorial, and by subsequent reviewers, larger prospective clinical trials are needed to understand the clinical utility of these approaches (Beanlands, 2019; Gould, 2013). Diagnostic accuracy of PET myocardial perfusion imaging, as compared to FFR as a reference standard, is limited to 15-oxygen (O)-water PET imaging, which is not available in the US (Takx, 2015). Most PET examinations are performed with 82-Rubidium (Rb) chloride instead, which has less favorable flow-extraction characteristics. Therefore, it is not possible to extrapolate the findings from 15O-water PET studies to clinical settings in which 82Rb-chloride is used.
 
The intervention of interest is quantitative cardiac PET perfusion imaging. Both MBF and myocardial flow reserve (MFR; defined as stress MBF/rest MBF) can be quantified. Generally, a MFR ≥ 2 is indicative of normal perfusion and is associated with a good prognosis (Bateman, 2021). Lower values of MFR may require further invasive testing to rule out epicardial CAD. As MFR decreases, the likelihood of multivessel obstructive CAD increases with a corresponding worsening prognosis.
 
Green et al conducted a meta-analysis on the prognostic value of MFR (called coronary flow reserve [CFR] in this analysis), as assessed by PET, for predicting adverse cardiovascular events in patients with suspected or known CAD (Green, 2021). The prognostic value of MFR was analyzed as a dichotomous variable (ie, impaired vs. preserved MFR); cut-off values used were as reported by the individual study. Thirteen studies (N=12,334) were identified. Four of the studies included patients with suspected CAD only; the remainder of the studies included a mixed population (suspected or known CAD). Eleven studies reported MACE outcomes, and the pooled HR for patients with impaired versus preserved MFR was 1.93 (95% CI, 1.65 to 2.27; I2=11%). Only 5 studies reported on hard events (ie, cardiac death, myocardial infarction) and there was significant heterogeneity (I2=72.8%); the pooled HR was 3.11 (95% CI, 1.88 to 5.14). Six studies included data useful to calculate separately the incidence rate of MACE events. The pooled incidence rate ratio for patients with impaired versus preserved MFR was 2.26 (95% CI, 1.79 to 2.85; I2=20.3%). Funnel plots for the MACE, but not hard events, indicated significant bias towards positive results. Publication bias may result in overstating the benefits of MFR prognostic value. Heterogeneity between studies and small sample sizes of some of the included studies further complicate interpretation. For instance, the cut-off value for designating an impaired MFR was not consistent across trials, stemming from differences in tracers, imaging protocols, and stress agents used in the studies. The authors note that due to the large heterogeneity in the study population, there is a need for further investigations to maximize the prognostic role of MFR.
 
Gould et al prospectively examined the relationship between regional, artery-specific MFR (called CFR in this analysis) and coronary flow capacity (CFC) and mortality in patients with suspected or known CAD who received and did not receive revascularization (Gould, 2021). Patients were recruited from a single center institution that routinely performs quantitative PET myocardial perfusion imaging in all patients with or at risk of CAD. CFC color maps are created using 5 color ranges for combined CFR and stress perfusion values of each pixel, which is mapped back to its location in the left ventricle. For the CFC maps, any with pixels that had both MFR ≤1.27 and stress perfusion ≤0.83 were defined as severely reduced CFC (CFCsevere). A total of 5274 patients were included in the cohort, who were followed for 4.2 years on average. Thirty-eight percent of patients had established CAD. Within 90 days of the PET scan, 245 patients (7.4%) received a coronary angiogram; of those patients, 76% underwent a revascularization procedure and 24% were deemed to not be appropriate candidates due to diffuse or complex CAD. Among the patients undergoing revascularization procedures (n=187), 152 (81%) were classified as CFCsevere and 35 (19%) were classified as moderately reduced CFC (no CFCsevere). Severely reduced regional MFR of 1.0 to 1.5 was associated with an increasing risk of all-cause death, myocardial infarction, stroke, or revascularization. Cox regression modeling showed that mortality risk was 54% lower (HR, 0.46; 95% CI, 0.26 to 0.79) after revascularization in patients classified as CFCsevere. For global assessments, patients with a global MFR <2.0 and global stress perfusion <1.8 had a significantly lower mortality risk with revascularization compared to no revascularization (p<.003). For other combinations with less severe global MFR or global stress perfusion, revascularization had no statistically significant impact on mortality risk. The authors note that generalizability may be a limitation as protocols, methodologies, and thresholds for intervention vary among institutions.
 
Studies evaluating the diagnostic performance of PET for cardiac sarcoidosis are limited by the absence of a gold standard reference (Chareonthaitawee, 2017). The Japanese Ministry of Health and Welfare (JMHW), the modified JMHW, or the Heart Rhythm Society diagnostic criteria are often used as the reference standard, but all have imperfect diagnostic accuracy.
 
Kim et al conducted a systematic review on the diagnostic performance of 18F-FDG PET or PET/CT for cardiac sarcoidosis (Kim, 2020). A total of 17 studies (N=891) were identified for inclusion. Thirteen studies were retrospectively designed, with the other 4 studies enrolling patients prospectively. The reference standards used in the included studies was the JMHW guideline or the modified JMHW. Across all studies, the pooled sensitivity was 84% (95% CI, 71% to 91%; I2=77.5) and the pooled specificity was 83% (95% CI, 74% to 89%; I2=80.0). The pooled sensitivity and specificity for the 6 studies that evaluated 18F-FDG PET alone was 92% (95% CI, 79% to 97%) and 66% (47% to 81%), respectively. The pooled sensitivity and specificity for the 11 studies that evaluated combination 18F-FDG PET/CT was 72% (95% CI, 66% to 78%) and 89% (86% to 92%), respectively. The overall positive likelihood ratio was 4.9 (95% CI, 3.3 to 7.3) and the negative likelihood ratio was 0.2 (95% CI, 0.11 to 0.35). The pooled diagnostic odds ratio was 27 (95% CI, 14 to 55). Pooled accuracy was assessed using a summary receiver operator characteristic curve; the area under the curve was 0.90 (95% CI, 0.87 to 0.92). The authors concluded that further large multicenter studies are necessary to substantiate the diagnostic accuracy of 18F-FDG PET for cardiac sarcoidosis.
 
The American Society of Nuclear Cardiology (ASNC) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) updated their joint guideline on procedure standards for cardiac PET procedures (Dilsizian, 2016). PET myocardial perfusion imaging is used "to detect physiologically significant coronary artery narrowing to guide clinical management of patients with known or suspected CAD [coronary artery disease] and those without overt CAD but with cardiovascular risk factors in order to: evaluate the progression of atherosclerosis, determine cause of ischemic symptoms and recommend medical or revascularization therapy, estimate the potential for future adverse events, and improve patient survival." Perfusion defects can be reported through qualitative scoring, semiquantitative scoring systems, or absolute quantification of myocardial blood flow (MBF). The guideline is limited by not providing direct recommendations with associated levels of evidence and strength of recommendations. However, the authors note that "quantitative absolute MBF measurements with PET appear most helpful in:
 
    • patients without known prior history of cardiac disease who present with symptoms suspicious for myocardial ischemia,
    • patients with known CAD, in whom more specific physiological assessment is desired,
    • identifying an increased suspicion for multivessel CAD,
    • situations with a disparity between visual perfusion abnormalities and apparently normal coronary angiography, in order to assess possible microvascular dysfunction, and
    • heart transplant when there is a question of vasculopathy.
 
In contrast, there are particular patients for whom reporting hyperemic blood flow or flow reserve may not add diagnostic value or can be ambiguous or misleading, including:
 
    • patients post-CABG [coronary artery bypass graft] who can have diffuse reduction on MBF despite patent grafts,
    • patients with large transmural infarcts where resting flow may be severely reduced such that small increases in flow lead to normal or near-normal flow reserve,
    • patients with advanced severe chronic renal dysfunction who likewise often have diffuse coronary disease, and
    • patients with severe LV [left ventricular] dysfunction."
 
A joint position paper from SNMMI/ASNC  further discussed clinical quantification of MBF (Murthy, 2018). Stress MBF and myocardial reserve flow (MFR) are associated with improved diagnostic sensitivity, but specificity has varied in studies. Treatment guidance noted that "[a]t present there are no randomized data supporting the use of any stress imaging modality for selection of patients for revascularization or for guidance of medical therapy. Observational data have established a paradigm that patients with greater degrees of ischemia on relative MPI [myocardial perfusion imaging] are more likely to benefit from revascularization. This paradigm has been conceptually extended to include MFR and stress MBF but has not yet been evaluated prospectively." The following key points were highlighted:
 
    • "Use of stress MBF and MFR for diagnosis is complex, as diabetes, hypertension, age, smoking, and other risk factors may decrease stress MBF and MFR without focal epicardial stenosis.
    • Patients with preserved stress MBF and MFR are unlikely to have high-risk epicardial CAD.
    • Preserved stress MBF of more than 2 mL/min/g and MFR of more than 2 reliably exclude the presence of high-risk angiographic disease (negative predictive value > 95%) and are reasonable to report when used in clinical interpretation.
    • A severely decreased global MFR (<1.5 mL/min/g) should be reported as a high-risk feature for adverse cardiac events but is not always due to multivessel obstructive disease. The likelihood of multivessel obstructive disease may be refined by examination of the electrocardiogram, regional perfusion, coronary calcification, and cardiac volumes and function.
    • Regional decreases in stress MBF (<1.5 mL/min/g) and MFR (<1.5) in a vascular territory may indicate regional flow-limiting disease."
 
The position paper additionally calls for further data on quantifying MBF and MFR in suspected or established CAD: "[t]hese methods are at the cusp of translation to clinical practice. However, further efforts are necessary to standardize measures across laboratories, radiotracers, equipment, and software. Most critically, data are needed supporting improved clinical outcomes when treatment selection is based on these measures."
 
A joint expert consensus document from SNMMI/ASNC covered the role of F-18 FDG PET for cardiac sarcoidosis detection and therapy monitoring (Chareonthaitawee, 2017). The document discusses the need to integrate multiple sources of data, including F-18 FDG PET in some cases, to diagnose cardiac sarcoidosis. The following outlines clinical scenarios where cardiac PET may be useful in patients with suspected or known disease. Associated levels of evidence and strength of recommendations were not provided with these scenarios.
 
    • "Patients with histologic evidence of extraCS [extracardiac sarcoidosis], and abnormal screening for CS [cardiac sarcoidosis], defined as one or more of following:
      • Abnormal electrocardiographic findings of complete left or right bundle branch block or presence of unexplained pathologic Q waves in two or more leads
      • Echocardiographic findings of regional wall motion abnormality, wall aneurysm, basal septum thinning, or LVEF [left ventricular ejection fraction] ≤ 50%
      • Holter findings of sustained or nonsustained ventricular tachycardia
      • Cardiac MRI findings suggestive of CS
      • Unexplained palpitations or syncope
    • Young patients (<60 y) with unexplained, new onset, significant conduction system disease (such as sustained second- or third-degree atrioventricular block)
    • Patients with idiopathic sustained ventricular tachycardia, defined as not fulfilling any of the following criteria:
      • Typical outflow tract ventricular tachycardia
      • Fascicular ventricular tachycardia
      • Ventricular tachycardia secondary to other structural heart disease (coronary artery disease or any cardiomyopathy other than idiopathic)
    • Patients with proven CS as adjunct to follow response to treatment"
 
A joint guidance from SNMMI/ACC/ASNC/AHA/Canadian Cardiovascular Society/Canadian Society of Cardiovascular Nuclear and CT Imaging/Society of Cardiovascular CT/American College of Physicians/European Association of Nuclear Medicine developed appropriate use criteria for PET myocardial perfusion imaging for the most common scenarios encountered (ACR, 2020). The summary of recommendations for patients with suspected or known CAD with symptoms state that rest-stress PET myocardial perfusion imaging is appropriate for those with an intermediate-to-high pretest likelihood of disease regardless of whether the patient has a normal electrocardiogram result or can (or cannot) exercise. In ordering tests, both the diagnostic accuracy and prognostic value are considerations. In patients with a low pretest likelihood of disease, PET myocardial perfusion imaging is not appropriate. The document also stated: "[o]nly a few studies describe the effects of PET MPI [myocardial perfusion imaging] perfusion and flow quantification on the clinical decision-making process and clinical outcome, which thus warrants further evaluation in well-designed and large-scale clinical trials."
 
For the evaluation of patients with known or suspected cardiac sarcoidosis, "rest PET MPI [myocardial perfusion imaging] was rated by the experts as appropriate in patients undergoing assessment of myocardial inflammation with 18F-FDG PET at baseline and during reevaluation for response to therapy or recurrent inflammation (Schindler 2020). In contrast, stress MPI was rated as may be appropriate in the evaluation of patients with suspected sarcoidosis who have not been previously evaluated for CAD, and as rarely appropriate in patients with suspected sarcoidosis who have been previously evaluated for CAD."
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2023. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
In 2021, the ASNC/SNMMI published a guide for interpretation and reporting of MBF with cardiac PET MPI to encourage and assist clinicians in the implementation of this relatively new approach to evaluate patients with known or suspected CAD (Bateman, 2021). The guide notes that "MBF evaluation provides complementary information to MPI that adds considerably to the value of the testing procedure in the diagnosis and risk stratification of CAD and cardiac events."
 
Per this guide, the clinical value of MBF reserve for patients with know CAD is as follows:
 
    • "Often abnormal after CABG, CAD history, myocardial infarction
    • Cardiomyopathy less useful but if normal, helps exclude CAD
    • Renal failure patients generally abnormal
    • Post PCI may be abnormal, but most useful if pre-PCI data available
    • Identify non-responder: all patients"
 
Aitken et al conducted a systematic review on the diagnostic performance of 18F-FDG PET or MRI for cardiac sarcoidosis (Aitken, 2022). Cardiac MRI was evaluated in 17 studies (n=1031) and 18F-FDG PET was evaluated in 26 studies (N=1363). Results demonstrated that cardiac MRI and 18F-FDG PET had similar specificity (85% vs. 82%; p=.85), but MRI demonstrated higher sensitivity (95% vs. 84%; p=.002).
 
In 2021, the ACC in collaboration with several other medical societies published a guideline on the evaluation and diagnosis of chest pain (Gulati, 2021). Per the guideline, after an acute coronary syndrome has been ruled out, PET or SPECT MPI allows for detection of perfusion abnormalities, measures of left ventricular function, and high-risk findings, such as transient ischemic dilation. The guideline goes on to state that: "For PET, calculation of myocardial blood flow reserve (MBFR, the ratio of peak hyperemia to resting myocardial blood flow) adds diagnostic and prognostic information over MPI data."
 
Effective January 1, 2022, the Centers for Medicare & Medicaid Services removed the umbrella national coverage determination (NCD) for PET Scans (CMS, 2022). In the absence of an NCD, coverage determinations for all oncologic and non-oncologic uses of PET that are not included in another NCD under section 220.6 will be made by the Medicare Administrative Contractors under section 1862(a)(1)(A) of the Social Security Act. All PET indications currently covered or non-covered under NCDs under section 220.6 remain unchanged and MACs shall not alter coverage for indications covered under NCDs.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
In 2023, the ACC and several other medical societies authored a guideline on management of chronic coronary disease (Virani, 2023). The guideline recommends PET or SPECT MPI, cardiovascular magnetic resonance imaging, or stress echocardiography, in patients with chronic coronary disease and a change in symptoms or functional capacity despite guideline-directed medical therapy (strong recommendation, moderate quality evidence). This testing facilitates detection of myocardial ischemia, estimation of the risk of major cardiovascular events, and therapeutic decisions. Preference is given to PET (over SPECT) due to greater diagnostic accuracy.
 
In 2023, the SNMMI published an expert panel consensus document on PET myocardial perfusion imaging for coronary microvascular dysfunction (Schindler, 2023). The document recommends PET imaging to detect coronary microvascular dysfunction in patients with chest pain but no evidence of CAD. Several scenarios are described that can facilitate test interpretation and application to therapeutic decision-making.
 
Additional 2024 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Ahmed et al conducted a meta-analysis of 21 studies (N=46,815) on the prognostic value of MFR, as assessed by PET, for predicting adverse cardiovascular events in patients with suspected or known CAD (Ahmed, 2023). Among the analyzed patients, 32% had known CAD. The results for the overall population of patients with suspected or known CAD demonstrated that impaired MFR was associated with a significantly increased risk of adverse outcomes (not specified) (RR, 2.94; 95% CI, 2.42 to 3.56; p<.001). Similar results were found in the subgroup of patients with suspected CAD, but a subgroup analysis of patients with known CAD was not reported.
 
Jensen et al conducted a meta-analysis of 19 studies on the prognostic value of MFR (called coronary flow reserve [CFR] in this analysis) in patients with non-obstructive CAD and coronary microvascular disease (Jensen, 2023). The analysis assessed CFR using PET, transthoracic echocardiography (TTE), and invasive coronary assessment for predicting adverse cardiovascular events. The results showed that the risk of death and MACE was significantly higher in patients with low CFR compared to those with normal CFR (OR, 3.23; 95% CI, 2.13 to 4.88; p<.001). For PET, the odds ratios (ORs) for the risk of death and MACE were 2.51 (95% CI, 1.40 to 4.49; p=.002) and 2.87 (95% CI, 2.16 to 3.81; p<.001), respectively. For TTE, the ORs for the risk of death and MACE were 4.25 (95% CI, 2.94 to 6.15; p<.001) and 6.98 (95% CI, 2.56 to 19.01; p<0.001), respectively. Lastly, for invasive intracoronary assessment, the ORs for the risk of death and MACE were 2.23 (95% CI, 1.15 to 4.34; p=.018) and 4.61 (95% CI, 2.51 to 8.48; p<.001), respectively.
 
The American Heart Association (AHA) published a scientific statement on the diagnosis and management of cardiac sarcoidosis (CS) in 2024 (Cheng, 2024). The statement notes, "FDG-PET is an integral tool in the evaluation and management of CS. FDG-PET is generally performed in conjunction with CMR to assess disease activity and monitor treatment response. FDG-PET should also be performed if a high pretest probability remains despite negative, nondiagnostic, or equivocal CMR results or in situations when CMR is contraindicated."
 
The American Society of Nuclear Cardiology (ASNC) published a PET model coverage policy in 2023 (Horgan, 2023). The document may be referred to for a comprehensive listing of clinical indications for conducting a cardiac PET study, along with supporting literature.
CPT/HCPCS:
78429Myocardial imaging, positron emission tomography (PET), metabolic evaluation study (including ventricular wall motion[s] and/or ejection fraction[s], when performed), single study; with concurrently acquired computed tomography transmission scan
78430Myocardial imaging, positron emission tomography (PET), perfusion study (including ventricular wall motion[s] and/or ejection fraction[s], when performed); single study, at rest or stress (exercise or pharmacologic), with concurrently acquired computed tomography transmission scan
78431Myocardial imaging, positron emission tomography (PET), perfusion study (including ventricular wall motion[s] and/or ejection fraction[s], when performed); multiple studies at rest and stress (exercise or pharmacologic), with concurrently acquired computed tomography transmission scan
78432Myocardial imaging, positron emission tomography (PET), combined perfusion with metabolic evaluation study (including ventricular wall motion[s] and/or ejection fraction[s], when performed), dual radiotracer (eg, myocardial viability);
78433Myocardial imaging, positron emission tomography (PET), combined perfusion with metabolic evaluation study (including ventricular wall motion[s] and/or ejection fraction[s], when performed), dual radiotracer (eg, myocardial viability); with concurrently acquired computed tomography transmission scan
78434Absolute quantitation of myocardial blood flow (AQMBF), positron emission tomography (PET), rest and pharmacologic stress (List separately in addition to code for primary procedure)
78459Myocardial imaging, positron emission tomography (PET), metabolic evaluation study (including ventricular wall motion[s] and/or ejection fraction[s], when performed), single study;
78491Myocardial imaging, positron emission tomography (PET), perfusion study (including ventricular wall motion[s] and/or ejection fraction[s], when performed); single study, at rest or stress (exercise or pharmacologic)
78492Myocardial imaging, positron emission tomography (PET), perfusion study (including ventricular wall motion[s] and/or ejection fraction[s], when performed); multiple studies at rest and stress (exercise or pharmacologic)
A9526Nitrogen n 13 ammonia, diagnostic, per study dose, up to 40 millicuries
A9552Fluorodeoxyglucose f 18 fdg, diagnostic, per study dose, up to 45 millicuries
A9555Rubidium rb 82, diagnostic, per study dose, up to 60 millicuries
References: Aitken M, Chan MV, Urzua Fresno C, et al.(2022) Diagnostic Accuracy of Cardiac MRI versus FDG PET for Cardiac Sarcoidosis: A Systematic Review and Meta-Analysis. Radiology. Sep 2022; 304(3): 566-579. PMID 35579526

Akaike G, Itani M, Shah H, et al.(2018) PET/CT in the Diagnosis and Workup of Sarcoidosis: Focus on Atypical Manifestations. Radiographics.Sep-Oct 2018; 38(5): 1536-1549. PMID 30118393

Authors/Task Force Members: McMurray JJ, Adamopoulos S, Anker SD et al.(2012) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012; 33(14):1787-847.

Bateman TM, Heller GV, Beanlands R, et al.(2021) Practical guide for interpreting and reporting cardiac PET measurements of myocardial blood flow: an Information Statement from the American Society of Nuclear Cardiology, and the Society of Nuclear Medicine and Molecular Imaging. J Nucl Med. Mar 31 2021. PMID 33789935

Bateman TM, Heller GV, Beanlands R, et al.(2021) Practical Guide for Interpreting and Reporting Cardiac PET Measurements of Myocardial Blood Flow: An Information Statement from the American Society of Nuclear Cardiology, and the Society of Nuclear Medicine and Molecular Imaging. J Nucl Med. Nov 2021; 62(11): 1599-1615. PMID 33789935

Bateman TM, Heller GV, McGhie AI, et al.(2006) Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99m sestamibi SPECT. J Nucl Cardiology 2006; 13(1):24-33.

Beanlands RS, Chow BJ, Dick A, et al.(2007) CCS/CAR/CANM/CNCS/CanSCMR joint position statement on advanced noninvasive cardiac imaging using positron emission tomography, magnetic resonance imaging and multidetector computed tomographic angiography in the diagnosis & evalutation of ischemic heart d Can J Cardiol 2007; 23(2):107-19.

Beanlands RS, Ziadi MC, Williams K.(2009) Quantification of myocardial flow reserve using positron emission imaging the journey to clinical use. J Am Coll Cardiol. Jul 07 2009; 54(2): 157-9. PMID 19573733

Beleslin DB, et al.(1994) Stress echocardiography in the detection of myocardial ischemia: head-to-head comparison of exercise, dobutamine, and dipyridamole tests. Circ 1994; 90:1168-1176.

Blue Cross and Blue Shield Association (BCBSA) Technology Evaluation Center (TEC).(1995) PET myocardial profusion imaging for the detection of coronary artery disease clinical assessment. TEC Assessments. 1995; Volume 10: Tab 21.

Centers for Disease Control and Prevention (CDC).(2022) Heart Disease Facts. Updated July 15, 2022. Accessed August 29, 2022. https://www.cdc.gov/heartdisease/facts.htm

Centers for Medicare & Medicaid Services (CMS).(2022) Positron Emission Tomography (PET) Scans. 2022; https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?ncdid=211. Accessed August 5, 2022.

Chareonthaitawee P, Beanlands RS, Chen W, et al.(2017) Joint SNMMI-ASNC Expert Consensus Document on the Role of 18 F-FDG PET/CT in Cardiac Sarcoid Detection and Therapy Monitoring. J Nucl Med. Aug 2017; 58(8): 1341-1353. PMID 28765228

Chen A, Wang H, Fan B, et al.(2017) Prognostic value of normal positron emission tomography myocardial perfusion imaging in patients with known or suspected coronary artery disease: a meta-analysis. Br J Radiol. Jun 2017;90(1074):20160702. PMID 28306335

Chou TM, et al.(1994) Evaluating CAD noninvasively: which test for whom? West J Med 1994; 161:173-180.

Churchwell KB, et al.(1994) The accuracy of PET rubidium-82 myocardial perfusion imaging to diagnose CAD: an objective quantitative analysis. J Nucl Med 1994; 35:23P.

Crouser ED, Maier LA, Wilson KC, et al.(2020) Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. Apr 15 2020; 201(8): e26-e51. PMID 32293205

Dai N, Zhang X, Zhang Y, et al.(2016) Enhanced diagnostic utility achieved by myocardial blood analysis: A meta-analysis of noninvasive cardiac imaging in the detection of functional coronary artery disease. Int J Cardiol. Oct 15 2016;221:665-673. PMID 27423088

Di Carli MF, Hachamovitch R.(2007) New technology for noninvasive evaluation of coronary artery disease. Circulation 2007; 115(11):1464-80.

Dilsizian V, Bacharach SL, Beanlands RS, et al.(2016) ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. J Nucl Cardiol. Oct 2016; 23(5): 1187-1226. PMID 27392702

Dweck MR, Abgral R, Trivieri MG, et al.(2017) Hybrid magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose to diagnose active cardiac sarcoidosis. JACC Cardiovasc Imaging. Jun 09 2017. PMID 28624396

Earls JP, White RD, Woodard PK et al.(2011) ACR Appropriateness Criteria(R) chronic chest pain--high probability of coronary artery disease. J Am Coll Radiol 2011; 8(10):679-86.

Fallavollita JA, Luisi AJ, Michalek SM, et al.(2006) Prediction of arrhythmic events with positron emission tomography: PAREPET study design Prand methods. Contemp Clin Trials 2006; 27(4):374-88.

Farhad H, Dunet V, Bachelard K, et al.(2013) Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging. Eur Heart J Cardiovasc Imaging. Dec 2013;14(12):1203-1210. PMID 23660750

FDA. PET drugs - current good manufacturing practice (CGMP) (small entity compliance guide), 08/2011. Available online at: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/ucm085783.htm. Last accessed June 2014.

FDA. PET drugs - current good manufacturing practice (CGMP), 12/10/2009. Available online at: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/ucm085783.htm. Last accessed June 2014.

Food and Drug Administration (FDA).(2012) Guidance: Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs. 2012; https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291573.pdf. Accessed July 26, 2021.

Fukushima K, Javadi MS, Higuchi T, et al.(2011) Prediction of short-term cardiovascular events using quantification of global myocardial flow reserve in patients referred for clinical 82Rb PET perfusion imaging. J Nucl Med. May 2011;52(5):726-732. PMID 21498538

Go R, et al.(1994) Current status of the clinical applications of cardiac PET. Radiol Clin N Am 1994; 32:501-519.

Gould KL, Johnson NP, Bateman TM et al.(2013) Anatomic Versus Physiologic Assessment of Coronary Artery Disease: Role of Coronary Flow Reserve, Fractional Flow Reserve, and Positron Emission Tomography Imaging in Revascularization Decision-Making. J Am Coll Cardiol 2013; 62(18):1639-53.

Gould KL, Johnson NP.(2015) Physiologic severity of diffuse coronary artery disease: hidden high risk. (2015b) Circulation. Jan 6 2015;131(1):4-6. PMID 25400061

Gould KL, Johnson NP.(2015) Physiologic stenosis severity, binary thinking, revascularization, and "hidden reality". (2015a) Circ Cardiovasc Imaging. Jan 2015;8(1). PMID 25596144

Gould KL, Kitkungvan D, Johnson NP, et al.(2021) Mortality Prediction by Quantitative PET Perfusion Expressed as Coronary Flow Capacity With and Without Revascularization. JACC Cardiovasc Imaging. May 2021; 14(5): 1020-1034. PMID 33221205

Green R, Cantoni V, Acampa W, et al.(2021) Prognostic value of coronary flow reserve in patients with suspected or known coronary artery disease referred to PET myocardial perfusion imaging: A meta-analysis. J Nucl Cardiol. Jun 2021; 28(3): 904-918. PMID 31875285

Gulati M, Levy PD, Mukherjee D, et al.(2021) 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. Nov 30 2021; 144(22): e368-e454. PMID 34709879

Gupta A, Taqueti VR, van de Hoef TP, et al.(2017) Integrated noninvasive physiological assessment of coronary circulatory function and impact on cardiovascular mortality in patients with stable coronary artery disease. Circulation. Dec 12 2017;136(24):2325-2336. PMID 28864442

Herzog BA, Husmann L, Valenta I, et al.(2009) Long-term prognostic value of 13N-ammonia myocardial perfusion positron emission tomography added value of coronary flow reserve. J Am Coll Cardiol. Jul 7 2009;54(2):150-156. PMID 19573732

Hoffmann R, Lethen H, Kleinhans E, et al.(1993) Comparative evaluation of bicycle and dobutamine stress echocardiography with perfusion scintigraphy and bicycle electrocardiogram for identification of coronary artery disease. Am J Card 1993; 72:555-559.

http://www.clinicaltrials.gov/ct2/show/NCT00321399?term=cardiac+sparc&rank=2 Last accessed December 2008.

Juarez-Orozco LE, Tio RA, Alexanderson E, et al.(2017) Quantitative myocardial perfusion evaluation with positron emission tomography and the risk of cardiovascular events in patients with coronary artery disease: a systematic review of prognostic studies. Eur Heart J Cardiovasc Imaging. Dec 27 2017. PMID 29293983

Kim SJ, Pak K, Kim K.(2020) Diagnostic performance of F-18 FDG PET for detection of cardiac sarcoidosis; A systematic review and meta-analysis. J Nucl Cardiol. Dec 2020; 27(6): 2103-2115. PMID 30603894

Klocke FJ, Baird MG, Lorell BH, et al.(2003) ACC/AHA/ASNC Guidelines for the clinical use of cardiac radionuclide imaging - a report of the ACC/AHA task force on paractice guidelines. J Am Coll Cardiol 2003; 42:1318.

Knesaurek K, Machac J.(2006) Comparison of 18F SPECT with PET in myocardial imaging: a realistic thorax-cardiac phantom study. BMC Nucl Med 2006; 6:5.

Knuuti J, Ballo H, Juarez-Orozco LE, et al.(2018) The performance of non-invasive tests to rule-in and rule-out significant coronary artery stenosis in patients with stable angina: a meta-analysis focused on post-test disease probability. Eur Heart J. May 29 2018. PMID 29850808

Maaniitty T, Stenstrom I, Bax JJ, et al.(2017) Prognostic value of coronary CT angiography with selective PET perfusion imaging in coronary artery disease. JACC Cardiovasc Imaging. Nov 2017;10(11):1361-1370. PMID 28528146

Mc Ardle B, Shukla T, Nichol G, et al.(2016) Long-term follow-up of outcomes with F-18-fluorodeoxyglucose positron emission tomography imaging-assisted management of patients with severe left ventricular dysfunction secondary to coronary disease. Circ Cardiovasc Imaging. Sep 2016;9(9). PMID 27609816

Merhige ME, Breen WJ, Shelton V, et al.(2007) Impact of myocardial perfusion imaging with PET and (82)Rb on downstream invasive procedure utilization, costs, and outcomes in coronary disease management. J Nucl Med 2007; 48(7):1069-76.

Murthy VL, Bateman TM, Beanlands RS, et al.(2018) Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC. J Nucl Med. Feb 2018; 59(2): 273-293. PMID 29242396

Parker MW, Iskandar A, Limone B et al.(2012) Diagnostic accuracy of cardiac positron emission tomography versus single photon emission computed tomography for coronary artery disease: a bivariate meta-analysis. Circ Cardiovasc Imaging 2012; 5(6):700-7.

Schindler TH, Bateman TM, Berman DS, et al(2020) Appropriate Use Criteria for PET Myocardial Perfusion Imaging. J Nucl Med. Aug 2020; 61(8): 1221-1265. PMID 32747510

Schindler TH, Fearon WF, Pelletier-Galarneau M, et al.(2023) Myocardial Perfusion PET for the Detection and Reporting of Coronary Microvascular Dysfunction: A JACC: Cardiovascular Imaging Expert Panel Statement. JACC Cardiovasc Imaging. Apr 2023; 16(4): 536-548. PMID 36881418

Schindler TH, Schelbert HR, Quercioli A, et al.(2010) Cardiac PET imaging for the detection and monitoring of coronary artery disease and microvascular health. JACC Cardiovasc Imaging. Jun 2010; 3(6): 623-40. PMID 20541718

Sharma S.(2009) Cardiac imaging in myocardial sarcoidosis and other cardiomyopathies. Curr Opin Pulm Med 2009; 15(5):507-12.

Siebelink HM, Blanksma PK, Crijns HJ, et al.(2001) No difference in cardiac event-free survival between positron emission tomography-guided and single-photon emission computed tomography-guided patient management: a prospective, randomized comparison of patients with suspicion of jeopardized myocardium. Am Coll Cardiol 2001; 37(1):81-8.

Siebelink HM, Blanksma PK, Crijns HJ, et al.(2001) No difference in cardiac event-free survival between positron emission tomography-guided and single-photon emission computed tomography-guided patient management: a prospective, randomized comparison of patients with suspicion of jeopardized myocardium. J Am Coll Cardiol. Jan 2001;37(1):81-88. PMID 11153777

Slart RH, Bax JJ, de Boer J, et al.(2005) Comparison of 99mTc-sestamibi/18FDG DISA SPECT with PET for the detection of viability in patients with coronary artery disease and left ventricular dysfunction. Eur J Nucl Med Mol Imaging 2005; 32(8):972-9.

Slart RH, Zeebregts CJ, Hillege HL, et al.(2011) Myocardial perfusion reserve after a PET-driven revascularization procedure: a strong prognostic factor. J Nucl Med. Jun 2011;52(6):873-879. PMID 21571798

Smulders MW, Jaarsma C, Nelemans PJ, et al.(2017) Comparison of the prognostic value of negative non-invasive cardiac investigations in patients with suspected or known coronary artery disease-a meta-analysis. Eur Heart J Cardiovasc Imaging. Feb 27 2017. PMID 28329376

Stuijfzand WJ, Uusitalo V, Kero T, et al.(2015) Relative flow reserve derived from quantitative perfusion imaging may not outperform stress myocardial blood flow for identification of hemodynamically significant coronary artery disease. Circ Cardiovasc Imaging. Jan 2015;8(1). PMID 25596142

Takx RA, Blomberg BA, El Aidi H, et al.(2015) Diagnostic accuracy of stress myocardial perfusion imaging compared to invasive coronary angiography with fractional flow reserve meta-analysis. Circ Cardiovasc Imaging. Jan 2015;8(1). PMID 25596143

Taqueti VR, Hachamovitch R, Murthy VL, et al.(2015) Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization. Circulation. Jan 6 2015;131(1):19-27. PMID 25400060

Tio RA, Dabeshlim A, Siebelink HM, et al.(2009) Comparison between the prognostic value of left ventricular function and myocardial perfusion reserve in patients with ischemic heart disease. J Nucl Med. Feb 2009;50(2):214-219. PMID 19164219

Virani SS, Newby LK, Arnold SV, et al.(2023) 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. Aug 29 2023; 82(9): 833-955. PMID 37480922

Waller AH, Blankstein R, Kwong RY, et al.(2014) Myocardial blood flow quantification for evaluation of coronary artery disease by positron emission tomography, cardiac magnetic resonance imaging, and computed tomography. Curr Cardiol Rep. May 2014; 16(5): 483. PMID 24718671

Wicks EC, Menezes LJ, Barnes A, et al.(2018) Diagnostic accuracy and prognostic value of simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in cardiac sarcoidosis. Eur Heart J Cardiovasc Imaging. Jul 1 2018;19(7):757-767. PMID 29319785

Xu J, Cai F, Geng C, et al.(2021) Diagnostic Performance of CMR, SPECT, and PET Imaging for the Identification of Coronary Artery Disease: A Meta-Analysis. Front Cardiovasc Med. 2021; 8: 621389. PMID 34026862

Yokoyama R, Miyagawa M, Okayama H, et al.(2015) Quantitative analysis of myocardial (18) F-fluorodeoxyglucose uptake by PET/CT for detection of cardiac sarcoidosis. Int J Cardiol. Sep 15 2015;195:180-187. PMID 26043154

Yokoyama R, Miyagawa M, Okayama H, et al.(2015) Quantitative analysis of myocardial (18)F-fluorodeoxyglucose uptake by PET/CT for detection of cardiac sarcoidosis. Int J Cardiol. Sep 15 2015;195:180-187. PMID 26043154

Youssef G, Leung E, Mylonas I et al.(2012) The use of 18F-FDG PET in the diagnosis of cardiac sarcoidosis: a systematic review and metaanalysis including the Ontario experience. J Nucl Med 2012; 53(2):241-8.

Youssef G, Leung E, Mylonas I, et al.(2012) The use of 18F-FDG PET in the diagnosis of cardiac sarcoidosis: a systematic review and metaanalysis including the Ontario experience. J Nucl Med. Feb 2012;53(2):241-248. PMID 22228794
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