Pending Policies - Radiology


Cardiac Applications of Positron Emission Tomography Scanning

Number:RAD605.001

Effective Date:11-15-2018

Coverage:

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Myocardial Perfusion Imaging

Cardiac positron emission tomography (PET) scanning may be considered medically necessary as a technique to assess myocardial perfusion defects when the patient has at least intermediate risk (See NOTE 1) for coronary artery disease AND the following criteria are met:

Indeterminate noninvasive imaging tests (e.g., single-photon emission computed tomography [SPECT] scan, myocardial perfusion imaging, stress echocardiogram); OR

Patients for whom SPECT could be reasonably expected to be suboptimal in quality due to body habitus, for example, including but not limited to:

o Moderate to severe obesity, i.e., body mass index (BMI) > 35 kg/m2; or

o Large breasts and/or implants; or

o Left mastectomy; or

o Chest wall deformity; or

o Any other technical problems (e.g., indeterminant prior SPECT, extensive prior myocardial infarction [MI], etc.).

NOTE 1: Intermediate risk is discussed in the Description section.

Myocardial Viability

Cardiac PET scanning may be considered medically necessary to assess the myocardial viability in patients with severe left ventricular dysfunction as a technique to determine candidacy for a revascularization procedure.

Cardiac Sarcoidosis

Cardiac PET scanning may be considered medically necessary for the diagnosis of cardiac sarcoidosis in patients who are unable to undergo magnetic resonance imaging (MRI) scanning. 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.

Quantification of Myocardial Blood Flow

Cardiac PET scanning is considered experimental, investigational and/or unproven for quantification of myocardial blood flow in patients diagnosed with coronary artery disease (CAD).

Description:

Positron Emission Tomography

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 greater spatial resolution.

Myocardial Perfusion Imaging

For myocardial perfusion studies, patient selection criteria for PET include individual assessment of the pretest probability of coronary artery disease (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 noninvasive 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 (25%-75% disease prevalence). (1) (See NOTE 2) Risk can be estimated using the patient’s age, sex, and chest pain quality. Table 1 summarizes patient populations at intermediate risk for CAD. (2)

Table 1. Individuals at Intermediate Risk for CAD According to Chest Pain Quality

Populations

Typical Anginaa

Atypical Anginab

Nonanginal Chest Painc

Men

30-39

30-70

≥50

Women

30-60

≥50

≥60

Values are age or age range in years.

CAD: coronary artery disease.

a 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.

b Chest pain that lacks one of the characteristics of typical angina.

c Chest pain that has one or none of the typical angina characteristics.

Body habitus can limit SPECT; particularly moderate-to-severe obesity, which can cause attenuation of tissue tracer leading to inaccurate images. In patients for whom body habitus is expected to lead to suboptimal SPECT scans, PET scanning is preferred.

NOTE 2: Intermediate-risk ranges used in different studies may differ from the range used here. These pretest probability risk groups are based on a 1995 Blue Cross Blue Shield Association Technology Evaluation Center (TEC) Assessment and take into account spectrum effect. 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%.

Myocardial Viability

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 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.

Comparison Between PET and SPECT

For both of the above indications, a variety of studies have suggested that PET scans are only marginally more sensitive or specific than SPECT scans. Therefore, the choice between a PET scan (which may not be available locally) and a SPECT scan presents another clinical issue. Table 2 summarizes differences between cardiac SPECT and PET techniques. (3)

Table 2. Advantages and Disadvantages of Cardiac PET and SPECT (3)

Imaging Technique

Advantages

Disadvantages

PET

Superior diagnostic capability, particularly for obese patients and patients with multivessel disease

Quantifiable blood flow evaluation

Integration of functional and anatomic information

Better spatial and contrast resolution

Lower frequency of artifacts

Higher equipment cost

Cyclotron or rubidium generators required

Radiotracers with short physical half-life do not permit exercise stress testing

SPECT

Wide availability

Well-established through published studies and familiar worldwide

Lower equipment cost

Less expensive radiotracers

Combined with dynamic exercise stress testing

Longer acquisition duration

Lower resolution images due to artifacts and attenuation

Higher radiation burden

PET: positron emission tomography; SPECT: single-photon emission computed tomography.

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. Radionuclides may be coupled with a variety of physiologically active molecules, such as oxygen, water, or ammonia. Fluorine 18 is often coupled with fluorodeoxyglucose to detect glucose metabolism, which in turn reflects metabolic activity, and thus viability, of the target tissue. Tracers that target the mitochondrial complex also are 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 for PET drug manufacturers, (4) and in August 2011, the FDA issued similar Current Good Manufacturing Practice guidance for small businesses. (5) 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. (6)

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 in Table 3.

Table 3. Radiopharmaceuticals Approved for Use With PET for Cardiac Indications

Date Approved

Radiopharmaceutical

Manufacturer

NDA

Cardiac-Related Indication With PET

2000

Fluorine 18 fluorodeoxyglucose (F-18-FDG)

Various

20306

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

2000

Ammonia N 13

Zevacor Pharma

22119

Imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing CAD

1989

Rubidium 82 Chloride

Bracco Diagnostics

19414

Assessing regional myocardial perfusion in the diagnosis and localization of myocardial infarction

CAD: coronary artery disease; NDA: new drug application; PET: positron emission tomography.

Rationale:

Assessment of a diagnostic technology typically focuses on 3 categories of evidence: 1) technical reliability (test-retest reliability or interrater reliability); 2) clinical validity (sensitivity, specificity, and positive and negative predictive value) in relevant populations of patients; and 3) clinical utility (i.e., demonstration that the diagnostic information can be used to improve patient outcomes). The following is a summary of the key literature to date.

Positron Emission Tomography

Clinical Context and Test Purpose

The purposes of positron emission tomography (PET) scanning in patients with suspected coronary artery disease (CAD), left ventricular (LV) dysfunction who are potential candidates for revascularization, CAD who require myocardial blood flow (MBF) quantification, and cardiac sarcoidosis are to confirm a diagnosis or to inform a clinician in disease management decisions.

The question addressed in this medical policy is: Does the use of PET improve the net health outcome in individuals with suspected CAD, LV dysfunction considering revascularization, CAD in need of MBF quantification, and cardiac sarcoidosis?

Patients

The population of interest includes patients with suspected CAD who have indeterminate single-photon emission computed tomography (SPECT) scans, severe LV dysfunction who are potential candidates for revascularization, CAD in need of quantifying MBF, and cardiac sarcoidosis who cannot undergo magnetic resonance imaging (MRI).

Interventions

The intervention of interest is PET scanning.

Comparators

The comparators of interest for each indication include:

For suspected CAD, coronary angiography or other noninvasive tests for CAD (e.g., stress echocardiography, exercise electrocardiography)

For severe LV dysfunction, cardiac MRI or cardiac SPECT scanning

For quantifying MBF in patients with CAD, coronary angiography with fractional flow reserve (FFR) or clinical risk models

For cardiac sarcoidosis, clinical evaluation or myocardial biopsy

Outcomes

For patients with suspected CAD, the outcome of interest is confirmed diagnosis. With a confirmed diagnosis, appropriate treatment options can be pursued.

For patients with severe LV dysfunction who are potential candidates for revascularization, the outcome of interest is a viability assessment. If there is sufficient viable myocardium detected, the patient would be a candidate for revascularization.

For patients with CAD who require MBF quantification, the outcome of interest is accurate quantification to inform clinical management of the disease.

For patients with suspected or diagnosed cardiac sarcoidosis, the outcome of interest is a diagnosis confirmation or an assessment of disease activity to inform clinical management of the disease.

Timing

For suspected CAD, MBF quantification, and suspected cardiac sarcoidosis, the timing of the test would be during the disease confirmation process. For severe LV dysfunction, the timing would be prior to surgical (revascularization) and clinical decision making.

Setting

The setting is an imaging center equipped with a PET scanner.

Suspected Coronary Artery Disease

Technical Reliability

In a patient with symptoms suggesting 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 [Rb-82]) and SPECT, have been investigated for identifying reversible perfusion defects, which may reflect CAD and thus identify patients appropriately referred for angiography.

The sensitivity and specificity of PET may be slightly better than for SPECT. Performance characteristics for PET and SPECT based on a 2007 Canadian joint position statement (7) are shown in Table 4.

Table 4. Performance Characteristics of PET and SPECT Based on the 2007 Position Statement (7)

Outcome Measures

PET

SPECT

Sensitivity

91%

88%

Specificity

89%

77%

Estimated positive likelihood ratioa

8.27

3.83

Estimated negative likelihood ratiob

0.10

0.16

PET: positron emission tomography; SPECT: single-photon emission computed tomography.

a Estimated positive likelihood ratio = sensitivity/(1 ? specificity).

b Estimated negative likelihood ratio = (1 ? sensitivity)/specificity.

However, diagnostic utilities of PET and SPECT may be similar in terms of modifying disease risk assessment in a manner that affects subsequent decision making in patients with intermediate pretest probability of CAD. For example, as shown in Table 5, a patient with a 50% pretest probability of CAD would have a 9% posttest probability of CAD after a negative PET scan compared with 13% probability after a negative SPECT. In either case, further testing may not be pursued.

Table 5. Diagnostic Utility (Effect on Pretest CAD Risk Assessment) of PET and SPECT

Pretest Probability

Posttest Probability, %

Positive Test

Negative Test

PET

SPECT

PET

SPECT

30%

78

62

4

6

50%

89

79

9

13

70%

95

90

19

27

CAD: coronary artery disease; PET: positron emission tomography; SPECT: single-photon emission computed tomography.

Clinical Validity

Systematic Reviews

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. (8) 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 2012, Jaarsma et al. reported on a meta-analysis comparing the diagnostic performance of noninvasive myocardial perfusion imaging using SPECT, cardiac MRI, or PET. (9) The comparison standard was CAD identified with coronary angiography. A total of 166 articles (N=17,901 patients) met inclusion criteria, with 114 articles on SPECT, 37 on cardiac MRI, and 15 on PET. Sensitivity by patient-level analysis was similar for the 3 tests, with a pooled sensitivity of 88% for SPECT, 89% for MRI, and 84% for PET. Pooled specificity was lower for SPECT (61%) compared with MRI (76%) or PET (81%). The pooled diagnostic odds ratio was 15.31 for SPECT, 26.42 for MRI, and 36.47 for PET. Meta-regression indicated that MRI and PET have a significantly higher diagnostic accuracy than SPECT. Although this analysis was limited by potential publication bias for SPECT and significant heterogeneity in the MRI and SPECT studies, most subgroup analyses have shown a relative superiority of MRI and PET over SPECT.

A second 2012 meta-analysis, by Parker et al., compared SPECT with PET stress myocardial perfusion imaging, using coronary angiography as the reference standard. (10) A total of 117 articles met selection criteria. SPECT was assessed in 113 studies (n=11,212 patients), and PET was assessed in 9 studies (n=650 patients). Patient-level diagnostic accuracy data were pooled in a bivariate meta-analysis, showing significantly better sensitivity for PET (92.6%) than for SPECT (88.3%). The difference in specificity between PET (81.3%) and SPECT (76.0%) was not significant. The pattern of higher sensitivity for PET over SPECT and similar specificity remained when analyses were limited to only high-quality studies.

Takx et al. (2015) reported a meta-analysis of studies that compared noninvasive myocardial perfusion imaging modalities (MRI, CT, PET, SPECT, echocardiography) with coronary angiography plus FFR. (11) Literature was searched to May 2014, and 37 studies met inclusion criteria (total 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 (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]). The area under the receiver operating characteristic (AUROC) analyses were similar at both the vessel level (PET, 0.95 vs SPECT, 0.83) and the patient level (PET, 0.93 vs SPECT, 0.82).

Another consideration is that there are fewer indeterminate results with PET than SPECT. Bateman et al. (2006) retrospectively matched 112 SPECT and 112 PET studies by sex, body mass index, and presence and extent of CAD, and compared diagnostic accuracy and degree of interpretative certainty (age, 65 years; 52% male; mean body mass index, 32 kg/m2; 76% with CAD diagnosed on angiography). (12) Eighteen (16%) of 112 SPECT studies were classified as indeterminate compared with 4 (4%) of 112 PET studies. Liver and bowel uptake were believed to affect 46 (41%) of 112 SPECT studies, compared with 6 (5%) of 112 PET studies. In obese patients (body mass index, >30 kg/m2), the accuracy of SPECT was 67% and 85% for PET; accuracy in non-obese patients was 70% for SPECT and 87% for PET. Therefore, for patients with intermediate pretest probability of CAD, one should start with SPECT testing and only proceed to PET in indeterminate cases. Also, because obese patients are more prone to liver and bowel artifact, PET testing is advantageous over SPECT in these patients.

Clinical Utility

Systematic Reviews

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. (13) 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. (14) 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.

Section Summary: Suspected Coronary Artery Disease

Evidence on the diagnostic accuracy of PET for CAD consists of several systematic reviews and meta-analyses. Meta-analyses comparing PET with reference standards such as coronary angiography and FFR have shown that PET is comparable in diagnostic accuracy. Meta-analyses that have evaluated the clinical utility of PET have looked at outcomes such as mortality and adverse cardiac events. These meta-analyses have shown that PET is a useful prognostic tool. For some patients in whom SPECT may be indeterminate due to body habitus or other anatomic factors, PET can be performed successfully.

Severe LV Dysfunction Considering Revascularization

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 nonviable. A fixed perfusion defect, as imaged on 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 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. 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 proportion of patients who experience improvement in LV dysfunction after revascularization of hibernating myocardium, as identified by PET scanning.

SPECT scanning also may be used to assess myocardial viability. Initial myocardial uptake of thallium 201 reflects myocardial perfusion, and redistribution after prolonged periods can be a marker of myocardial viability. Initial protocols required redistribution imaging after 24 to 72 hours. Although this technique was associated with a strong positive predictive value, there was a low NPV; i.e., 40% of patients without redistribution nevertheless showed clinical improvement after revascularization. NPVs have 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.

Clinical Validity

Studies identified in literature have shown the equivalence of SPECT and PET in their ability to assess myocardium viability. Comparative studies have reported on test accuracy and have not addressed the impact on clinical outcomes. Using a thorax-cardiac phantom with different sized inserts that simulated infarcts, Knesaurek and Machac (2006) tested SPECT and PET images. (15) The investigators concluded that PET was better at detecting smaller defects than SPECT. In this study, a 1-cm insert, not detected by SPECT, was detected by PET.

Slart et al. (2005) compared dual-isotope simultaneous acquisition SPECT and PET in the detection of myocardial viability in 58 patients with CAD and dysfunctional LV myocardium. (16) Tracer uptake for PET and SPECT was compared by linear regression and correlation analysis, which showed that there was overall good agreement between SPECT and PET for the assessment of myocardial viability in patients with severe LV dysfunction.

Clinical Utility

Randomized Controlled Trials

A large randomized controlled trial, Positron Emission Tomography and Recovery Following Revascularization (PARR-2), evaluated the impact of FDG-PET viability imaging on patients with severe LV dysfunction. Patients from 9 sites were randomized to FDG-PET-assisted physician management (n=218) or standard care management by a physician without PET imaging available (n=212). Management decision options were: revascularization, revascularization workup, or neither. The primary outcome was a composite of cardiac death, myocardial infarction, or recurrent hospital stay for a cardiac cause. Beanlands et al. (2007) reported on results after 1 year of follow-up. (17) The intention-to-treat hazard ratio (HR) of a composite event occurring at 1 year was not significant (0.78; 95% CI, 0.58 to 1.1; p=0.15) for PET-assisted management of care compared with standard care. However, among patients in the PET-assisted management of care group who had high or medium myocardium viability and who therefore were recommended to receive revascularization or a revascularization workup, 26% did not ultimately receive the recommended care. Reasons given included symptoms stabilizing, renal failure, multiple comorbidities, and patient refusal. When subgroup analysis included only those patients who received the treatment as recommended based on PET images, the HR for a composite event was significant (0.62; 95% CI, 0.42 to 0.93).

In 2016, McArdle et al. published long-term follow-up results for PARR-2. (18) 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. (19) 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.

Nonrandomized Study

In 2016, Srivatsava et al. published a study of 120 patients with LV dysfunction who underwent both SPECT-CT and FDG-PET/CT to determine myocardial viability. (20) If both tests showed defects, the tissue was considered nonviable. If test results were mismatched, the tissue was considered hibernating but viable. If more than 7% of the myocardium was considered viable, patients underwent revascularization by either stenting or CABG (78 patients). Patients assessed as having less than 7% viable myocardium were medically managed (42 patients). The primary outcome was global left ventricular ejection fraction (LVEF). Change in LVEF after 3 months was significantly larger in the surgically managed group (3.5; 95% CI, 2.5 to 4.5) than in the medically managed group (0.7; 95% CI, -0.8 to 2.2).

Section Summary: Severe LV Dysfunction Considering Revascularization

Evidence for the use of PET to assess myocardial viability consists of a large randomized controlled trial that randomized patients with LV dysfunction into 2 groups: one was managed by physicians receiving PET images to inform care decisions, and the other was managed by physicians who did not receive PET images. Follow-up at 1 year and 5 years showed that when patients received care as indicated by the PET images, they were at decreased risk for cardiac death, myocardial infarction, or recurrent hospital stay compared with patients who did not. Available evidence from smaller trials has suggested that the accuracy of PET and SPECT are roughly similar for this purpose. PET may be more sensitive regarding small defects, but the clinical significance of identifying small defects is uncertain.

Myocardial Blood Flow Quantification

Several publications have described the use of PET imaging to quantify both MBF and myocardial flow reserve (MFR; defined as stress MBF/rest MBF). (21, 22) However, as noted in an accompanying editorial (23) and by subsequent reviewers, (24) larger prospective clinical trials are needed to understand the clinical utility of these approaches.

Clinical Validity

In 2017, Hsu et al. published a study comparing SPECT with N 13 ammonia PET in blood flow quantitation. (25) Healthy patients (n=12) and patients with CAD (n=16) underwent both SPECT and N 13 ammonia PET flow scans. MFR measures by SPECT and PET did not differ significantly in healthy patients. The MFR measures were also comparable in patients with CAD. The authors concluded that MFR can be accurately measured by either modality.

Stuijfzand et al. (2015) used oxygen 15-labelled water PET imaging in 92 patients with 1-2 vessel disease to quantify MBF, MFR, and “relative flow reserve” (defined as stress MBF in a stenotic area/stress MBF in a normal perfused area). (26) 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), area under the curve (AUC) analysis showed similar diagnostic performance for all 3 measures (0.76 [95% CI, 0.66 to 0.86] for MBF; 0.72 [95% CI, 0.61 to 0.83] for MFR; 0.82 [95% CI, 0.72 to 0.91] for relative flow reserve; p>0.05 for all comparisons).

Clinical Utility

Taqueti et al. (2015) evaluated the association between MFR (called coronary flow reserve [CFR] in this study) and cardiovascular outcomes in 329 consecutive patients referred for invasive coronary angiography after stress PET perfusion imaging. (27) Patients with a history of CABG or heart failure, or with LVEF less than 40%, were excluded. Patients underwent Rb-82 or N 13 ammonia PET imaging and selective coronary angiography. MFR was calculated as the ratio of stress to rest MBF 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 MBF 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 MACE (comprising death, cardiovascular death, and hospitalization for heart failure or myocardial infarction). During follow-up, 64 (19%) patients 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 Coronary Artery Disease Prognostic Index, 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). The model used binary classification defined by median MFR; and the 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), percutaneous coronary intervention (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 percutaneous coronary intervention group (n=85; p=0.006) and the no-revascularization group (n=57; p=0.001).

In 2011, Ziadi et al. reported on a prospective study of the prognostic value of MFR with Rb-82 PET in 704 consecutive patients assessed for ischemia. (28) Ninety-six percent (n=677) of patients were followed for a median of 387 days; most (90%) were followed by telephone. The hypothesis tested was that patients with reduced flow reserve would have higher cardiac event rates and that Rb-82 MFR would be an independent predictor of adverse outcomes. The primary outcome was the prevalence of hard cardiac events (myocardial infarction and cardiac death); the secondary outcome was the prevalence of MACE (comprising cardiac death, myocardial infarction, later revascularization, and cardiac hospitalization). Patients with a normal summed stress score but impaired MFR had a significantly higher incidence of hard events (2% vs 1.3%) and MACE (9% vs 3.8%) compared with patients who had preserved MFR. Patients with abnormal summed stress score and impaired MFR had a higher incidence of hard events (11.4% vs 1.1%) and MACE (24% vs 9%) compared with patients who had preserved MFR. Rb-82 MFR was an independent predictor of cardiac hard events (HR=3.3) and MACE (HR=2.4) over summed stress score. Three (0.4%) patients were classified up and 0 were classified down with MFR in the multivariate model (p=0.092).

Murthy et al. (2011) examined the prognostic value of Rb-82 PET MFR (called CFR in this study) in a retrospective series of 2783 patients referred for rest/stress PET myocardial perfusion imaging. (29) CFR was calculated as the ratio of stress to rest MBF using semi-quantitative PET interpretation. The primary outcome was cardiac death over a median follow-up of 1.4 years. Prognostic modeling was done with a Cox proportional hazards model. Adding MFR to a multivariate model containing clinical covariates (e.g., CAD risk factors and CAD history) significantly improved model fit and improved the c index, a measure of discrimination performance, from 0.82 to 0.84 (p=0.02). MFR was a significant independent predictor of cardiac mortality and resulted in improved risk reclassification. In 2012, these authors reported that the added value of PET MFR was observed in both diabetic and nondiabetic patients. (30)

Section Summary: Myocardial Blood Flow Quantification

Evidence is growing for the association of quantitative MBF and MFR with cardiovascular outcomes. 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. (31, 32) 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.

Cardiac Sarcoidosis

Based on clinical input received in 2011, an additional indication for the workup of cardiac sarcoidosis was added to the evidence review. There is no standard diagnostic criterion for cardiac sarcoidosis. The latest consensus statement (2014) issued by the Heart Rhythm Society (HRS) stated that if a histologic diagnosis along with at least 1 clinical symptom (e.g., reduced LVEF, heart block, patchy uptake of FDG-PET, late gadolinium enhancement on cardiac MRI, or cardiomyopathy) were present, the patient had a 50% or greater likelihood of cardiac sarcoidosis. (33) Currently, clinicians are combining clinical data with imaging techniques (cardiac MRI and FDG-PET) to make a diagnosis.

Clinical Validity

Systematic Reviews

In 2016, Tang et al. published a systematic review on the overall diagnostic performance of FDG-PET/CT in cardiac sarcoidosis, and on subgroups based on the type of patient preparation methods (fasting time, heparin administration, diet). (34) The literature search, conducted through August 2014, identified 16 nonrandomized studies (total N=559 patients) for inclusion. Study quality was assessed using QUADAS-2, with most studies having a low risk of bias. Overall sensitivity and specificity, when a large single study with a short fasting duration was excluded, were 81% (95% CI, 76% to 86%) and 82% (95% CI, 77% to 86%), respectively. Subgroup analyses based on the type of patient preparation method showed that the diagnostic odds ratio improved when patients fasted longer (≥12 hours) and heparin was administered. Placing the patient on a high-fat, low-carbohydrate diet before scanning did not affect the diagnostic accuracy of FDG-PET/CT.

A 2012 meta-analysis by Youssef et al. identified 7 studies (total N=164 patients). (35) 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.

A 2009 review by Sharma reported that cardiac MRI was the more established imaging modality in diagnosing sarcoidosis, with an estimated sensitivity of 100% and specificity of 80%. Studies using FDG-PET showed high sensitivities; however, the population sizes of the studies were small. The reviewer asserted that imaging studies had incremental value when combined with clinical evaluation and/or myocardial biopsy in the diagnosis of cardiac sarcoidosis and called for additional research on the role of MRI and/or PET for this use. (36)

Nonrandomized Studies

In 2016, Lapa et al. published a study to determine whether PET/CT using radiolabeled somatostatin receptor (SSRT) ligands for visualization of inflammation would accurately diagnose cardiac sarcoidosis. (37) Fifteen patients with sarcoidosis and suspicion of cardiac involvement underwent both SSTR-PET/CT and cardiac MRI. Concordant results between PET/CT and MRI occurred in 12 of the 15 patients.

In 2017, Dweck et al. published a study evaluating the usefulness of a hybrid of cardiac MRI and FDG- PET to diagnose cardiac sarcoidosis. (38) 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. (39)

Clinical Utility

No studies evaluating the clinical utility of using PET or PET/CT in diagnosing cardiac sarcoidosis were identified.

Section Summary: Cardiac Sarcoidosis

Left untreated, cardiac sarcoidosis can lead to serious developments such as arrhythmia, heart failure, pericarditis, and heart attacks. However, there is no criterion standard for diagnosing cardiac sarcoidosis. A combination of clinical evaluations and results from imaging techniques are used in the clinician’s assessment. Results from 2 meta-analyses have shown that PET can be a useful tool in this diagnostic process. Since the meta-analyses, small nonrandomized studies have been published that evaluated variations in PET techniques such as using a radiolabeled SSRT ligand and adding a simultaneous cardiac MRI. These studies have shown positive results.

Summary of Evidence

For individuals with suspected coronary artery disease and an indeterminate single-photon emission computed tomography (SPECT) scan who receive positron emission tomography (PET), the evidence includes several systematic reviews and meta-analyses. Relevant outcomes are test accuracy and disease-specific survival. Meta-analyses of studies in which PET results were compared with results from coronary angiography and fractional flow reserve have shown that PET is comparable in diagnostic accuracy to these referent standards. In meta-analyses of studies that included clinical outcomes such as mortality and adverse cardiac events, results have shown that PET is a useful prognostic tool. Subgroup analyses have shown that PET can be useful in patients whose body habitus is likely to result in indeterminate SPECT scans (e.g., patients with moderate to severe obesity). The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals with left ventricular dysfunction who are potential candidates for revascularization who undergo cardiac PET scanning to assess myocardial viability, the evidence includes a large randomized controlled trial with long-term follow-up and several small trials comparing SPECT with PET. Relevant outcomes are test accuracy and morbid events. In the large randomized controlled trial, patients with left ventricular dysfunction were randomized to care from physicians who would make management decisions based on PET images to care from physicians who would make management decisions without PET images. At 1- and 5-year follow-ups, patients who received care indicated by the PET images were at decreased risk for cardiac death, myocardial infarction, and recurrent hospital stays compared with patients who did not. The trials comparing SPECT with PET showed that both modalities were useful in managing patients considering revascularization. Evidence-based recommendations from specialty societies have concluded that PET scanning is at least as good as, and likely superior, to SPECT scanning for this purpose. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals with coronary artery disease who require myocardial blood flow quantification who receive quantitative cardiac PET, the evidence includes observational studies. The relevant outcome is morbid events. Studies adding PET-derived quantitative myocardial blood flow and myocardial flow reserve to prognostic models of clinical risk factors for cardiac events have reported inconsistent results, indicating that these methods are in a developmental stage for clinical use. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals with suspected or diagnosed cardiac sarcoidosis who require evaluation who receive cardiac PET, the evidence includes systematic reviews and meta-analyses. The relevant outcome is test accuracy. Currently, there is no criterion standard for diagnosing cardiac sarcoidosis. A combination of clinical evaluations and results from imaging techniques, usually magnetic resonance imaging (MRI), are used during the clinician’s assessment. The pooled results from meta-analyses have shown good sensitivity, specificity, and area under the curve estimates. Several small studies have evaluated variations in PET techniques such as using a radiolabeled somatostatin receptor ligand and adding a simultaneous cardiac MRI. Reported results were positive in these small studies, but larger samples are needed to confirm the usefulness of these changes. While MRI is the imaging technique most often used to evaluate cardiac sarcoidosis, for patients who are unable to undergo MRI (e.g., patients with a metal implant), evidence supports PET scanning as the preferred test. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Practice Guidelines and Position Statements

American College of Cardiology

In 2003, the American College of Cardiology, American Heart Association, and American Society for Nuclear Cardiology updated their joint guidelines for cardiac radionuclide imaging, including cardiac applications of positron emission tomography (PET). (40) Table 6 summarizes the guidelines for PET and single-photon emission computed tomography (SPECT) imaging in patients with an intermediate risk of coronary artery disease (CAD).

Table 6. Guidelines for PET and SPECT in Patients With Intermediate Coronary Artery Disease Risk (40)

Indication

Class

SPECT

PET

Identify extent, severity, and location of ischemia (SPECT protocols vary according to whether patient can exercise)

I

IIa

Repeat test after 3-5 y after revascularization in selected high-risk asymptomatic patients (SPECT protocols vary according to whether patients can exercise)

IIa

-

As initial test in patients who are considered to be at high risk (i.e., patients with diabetes or those with a >20% 10-y risk of a coronary disease event) (SPECT protocols vary according to whether patients can exercise)

IIa

-

Myocardial perfusion PET when prior SPECT study has been found to be equivocal for diagnostic or risk stratification purposes

Not appropriate

I

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.

PET: positron emission tomography; SPECT: single-photon emission computed tomography.

These guidelines concluded that PET “appears to have slightly better overall accuracy for predicting recovery of regional function after revascularization in patients with left ventricular dysfunction than single-photon techniques (i.e., SPECT scans).” (40) However, the guidelines indicated that either PET or SPECT scans are class I indications for predicting improvement in regional and global left ventricular function and natural history after revascularization; therefore, the guidelines did not indicate a clear preference for PET or SPECT scans in this situation.

In 2009, the American College of Cardiology and American Heart Association collaborated with 6 other imaging societies to develop Appropriate Use Criteria for cardiac radionuclide imaging (RNI). (41) Their report stated:

“…use of cardiac RNI for diagnosis and risk assessment in intermediate- and high-risk patients with coronary artery disease (CAD) was viewed favorably, while testing in low-risk patients, routine repeat testing, and general screenings in certain clinical scenarios were viewed less favorably. Additionally, use for perioperative testing was found to be inappropriate except for high selected groups of patients.”

Canadian Cardiovascular Society et al.

In 2007, Canadian Cardiovascular Society and 4 other Canadian imaging societies recommended PET scanning for patients with intermediate pretest probability of CAD who have non-diagnostic noninvasive imaging tests, or where such a test does not agree with clinical diagnosis or may be prone to artifact that could lead to another, equivocal test, e.g., obesity (class I recommendation, level B evidence). (7)

American College of Radiology

The 2011 American College of Radiology (ACR) Appropriateness Criteria considered both SPECT and PET to be appropriate for the evaluation of patients with a high probability of CAD. (42) The ACR indicated that PET perfusion imaging has advantages over SPECT, including higher spatial and temporal resolution. Routine performance of both PET and SPECT are unnecessary. The 2017 update (43) stated:

“Hybrid PET scanners use CT [computed tomography] for attenuation correction (PET/CT) following completion of the PET study. By coupling the PET perfusion examination findings to a CCTA [coronary computed tomographic angiography], PET/CT permits the fusion of anatomic coronary arterial and functional (perfusion) myocardial information and enhances diagnostic accuracy. The fused examinations can accurately measure the atherosclerotic burden and identify the hemodynamic functional significance of coronary stenosis. The results of the combined examinations can more accurately identify patients for revascularization.”

The 2012 ACR Appropriateness Criteria also recommended PET for the evaluation of patients with chronic chest pain and low-to-intermediate probability of CAD. (44)

ACR does not recommend PET for patients with acute nonspecific chest pain who have low probability of CAD (45) or for asymptomatic patients at risk for CAD. (46)

European Society of Cardiology

European Society of Cardiology published evidence-based consensus guidelines on the diagnosis and treatment of acute and chronic heart failure in 2012. (47) In 2016, the Society updated its guidelines, reaffirming the use of SPECT for assessment of ischemia and myocardial viability to consider suitability for coronary revascularization. (48) Additional revisions indicated that:

“Echocardiography is the method of choice in patients with suspected heart failure, for reasons of accuracy, availability and safety… Gated SPECT can also yield information on ventricular volumes and function, but exposes the patient to ionizing radiation. Positron emission tomography (PET) (alone or with CT) may be used to assess ischemia and viability, but the flow tracers (N-13 ammonia or O-15 water) require an on-site cyclotron. Rubidium is an alternative tracer for ischemia testing with PET. Limitations include radiation exposure for PET imaging.”

Japanese Society of Nuclear Cardiology

In 2014, the Japanese Society of Nuclear Cardiology published recommendations on PET for cardiac sarcoidosis. (49) In Japan, fluorine 18 fluorodeoxyglucose PET (FDG-PET) is approved only for detecting sites of inflammation in cardiac sarcoidosis. In patients with cardiac sarcoidosis diagnosed by established guidelines (e.g., 2006 update of Japanese Ministry of Health and Welfare guidelines), FDG-PET may be used to assess lesion distribution. However, use of FDG-PET to diagnose patients with suspected cardiac sarcoidosis is not covered by the health ministry’s insurance reimbursement.

U.S. Preventive Services Task Force Recommendations

No U.S. Preventive Services Task Force recommendations for the use of PET in cardiac imaging have been identified.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 7.

Table 7. Summary of Key Trials

NCT No.

Trial Name

Planned Enrollment

Completion Date

Ongoing

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)

1511

Sep 2017

NCT01434043

Diagnostic Accuracy of Cardiac CT Perfusion Compared to PET Imaging

30

Dec 2017

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)

1511

Mar 2018

NCT00756379

Randomized Trial of Comprehensive Lifestyle Modifications, Optimal Pharmacological Treatment and PET Imaging for Detection and Management of Stable Coronary Artery Disease

1300

Jan 2019

NCT03103490

18F-FSPG PET/MRI Imaging of Cardiac Sarcoidosis or Inflammation

20

Apr 2020

Unpublished

NCT01934985

Dynamic Cardiac SPECT Imaging

160

unknown

NCT01109992

Integrated Dual Exercise and Lexiscan PET: (IDEALPET)

41

Jun 2017 (completed)

NCT: national clinical trial.

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Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

0482T, 78459, 78491, 78492

HCPCS Codes

A9526, A9552, A9555

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.

A national coverage position for Medicare may have been changed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

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12. Bateman TM, Heller GV, McGhie AI, et al. Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99m sestamibi SPECT. J Nucl Cardiol. Jan-Feb 2006; 13(1):24- 33. PMID 16464714

13. Chen A, Wang H, Fan B, et al. 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

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17. Beanlands RS, Nichol G, Huszti E, et al. F-18-fluorodeoxyglucose positron emission tomography imaging- assisted management of patients with severe left ventricular dysfunction and suspected coronary disease: a randomized, controlled trial (PARR-2). J Am Coll Cardiol. Nov 13 2007; 50(20):2002-2012. PMID 17996568

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19. Siebelink HM, Blanksma PK, Crijns HJ, et al. 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

20. Srivatsava MK, Indirani M, Sathyamurthy I, et al. Role of PET-CT in the assessment of myocardial viability in patients with left ventricular dysfunction. Indian Heart J. Sep - Oct 2016; 68(5):693-699. PMID 27773409

21. Herzog BA, Husmann L, Valenta I, et al. 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

22. Schindler TH, Schelbert HR, Quercioli A, et al. Cardiac PET imaging for the detection and monitoring of coronary artery disease and microvascular health. JACC Cardiovasc Imaging. Jun 2010; 3(6):623-640. PMID 20541718

23. Beanlands RS, Ziadi MC, Williams K. Quantification of myocardial flow reserve using positron emission imaging the journey to clinical use [editorial]. J Am Coll Cardiol. Jul 7 2009; 54(2):157-159. PMID 19573733

24. Gould KL, Johnson NP, Bateman TM, et al. 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. Oct 29 2013; 62(18):1639-1653. PMID 23954338

25. Hsu B, Hu LH, Yang BH, et al. SPECT myocardial blood flow quantitation toward clinical use: a comparative study with 13N-Ammonia PET myocardial blood flow quantitation. Eur J Nucl Med Mol Imaging. Jan 2017; 44(1):117-128. PMID 27585576

26. Stuijfzand WJ, Uusitalo V, Kero T, et al. 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

27. Taqueti VR, Hachamovitch R, Murthy VL, et al. 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

28. Ziadi MC, Dekemp RA, Williams KA, et al. Impaired myocardial flow reserve on rubidium-82 positron emission tomography imaging predicts adverse outcomes in patients assessed for myocardial ischemia. J Am Coll Cardiol. Aug 9 2011; 58(7):740-748. PMID 21816311

29. Murthy VL, Naya M, Foster CR, et al. Improved cardiac risk assessment with noninvasive measures of coronary flow reserve. Circulation. Nov 15 2011; 124(20):2215-2224. PMID 22007073

30. Murthy VL, Naya M, Foster CR, et al. Association between coronary vascular dysfunction and cardiac mortality in patients with and without diabetes mellitus. Circulation. Oct 9 2012; 126(15):1858-1868. PMID 22919001

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

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

33. Birnie DH, Sauer WH, Bogun F, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm. Jul 2014; 11(7):1305-1323. PMID 24819193

34. Tang R, Wang JT, Wang L, et al. Impact of patient preparation on the diagnostic performance of 18f-FDG PET in cardiac sarcoidosis: a systematic review and meta-analysis. Clin Nucl Med. Jul 2016; 41(7):e327-339. PMID 26646995

35. Youssef G, Leung E, Mylonas I, et al. 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

36. Sharma S. Cardiac imaging in myocardial sarcoidosis and other cardiomyopathies. Curr Opin Pulm Med. Sep 2009; 15(5):507-512. PMID 19542892

37. Lapa C, Reiter T, Kircher M, et al. Somatostatin receptor based PET/CT in patients with the suspicion of cardiac sarcoidosis: an initial comparison to cardiac MRI. Oncotarget. Nov 22 2016; 7(47):77807-77814. PMID 27780922

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

39. Yokoyama R, Miyagawa M, Okayama H, et al. 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

40. Klocke FJ, Baird MG, Lorell BH, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). J Am Coll Cardiol. Oct 1 2003; 42(7):1318-1333. PMID 14522503

41. Hendel RC, Berman DS, Di Carli MF, et al. ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging: A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, and the Society of Nuclear Medicine. J Am Coll Cardiol. Jun 09 2009; 53(23):2201-2229. PMID 19497454

42. Earls JP, White RD, Woodard PK, et al. ACR Appropriateness Criteria(R) chronic chest pain--high probability of coronary artery disease. J Am Coll Radiol. Oct 2011; 8(10):679-686. PMID 21962781

43. Expert Panel on Cardiac Imaging, Akers SR, Panchal V, et al. ACR Appropriateness Criteria(R) Chronic Chest Pain-High Probability of Coronary Artery Disease. J Am Coll Radiol. May 2017; 14(5S):S71-S80. PMID 28473096

44. American College of Radiology (ACR). ACR Appropriateness Criteria: Chronic Chest Pain - Low to Intermediate Probability of Coronary Artery Disease. 2012. Available at <https://acsearch.acr.org> (accessed August 3, 2017).

45. American College of Radiology (ACR). ACR Appropriateness Criteria: Acute Nonspecific Chest Pain--Low Probability of Coronary Artery Disease. 2015. Available at <https://acsearch.acr.org> (accessed August 3, 2017).

46. American College of Radiology (ACR). ACR Appropriateness Criteria: Asymptomatic Patient at Risk for Coronary Artery Disease. 2013. Available at <https://acsearch.acr.org> (accessed August 3, 2017).

47. McMurray JJ, Adamopoulos S, Anker SD, et al. 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. Jul 2012; 33(14):1787-1847. PMID 22611136

48. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. Aug 2016; 18(8):891-975. PMID 27207191

49. Ishida Y, Yoshinaga K, Miyagawa M, et al. Recommendations for (18)F-fluorodeoxyglucose positron emission tomography imaging for cardiac sarcoidosis: Japanese Society of Nuclear Cardiology Recommendations. Ann Nucl Med. May 2014; 28(4):393-403. PMID 24464391

50. Cardiac Applications of Positron Emission Tomography Scanning. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2017 September) Radiology 6.01.20.

Policy History:

Date Reason
11/15/2018 Reviewed. No changes.
12/1/2017 Document updated with literature review. Policy content modified to address only cardiac applications of PET, without change to Coverage. Information on oncologic and other miscellaneous applications of PET, in addition to positron emission mammography, can now be found in eviCore guidelines. Modified language in Description related to risk assessment ratings for coronary heart disease. Title changed from: Positron Emission Tomography (PET).
4/15/2017 Reviewed. No changes.
3/1/2016 Document updated with literature review. The following coverage language criterion, specific to lymphoma was changed under subsequent treatment strategy planning for oncologic indications to now read: “PET or PET/CT imaging for subsequent treatment strategy planning may be considered medically necessary when the initial diagnostic PET criteria were met and PET is needed: for the purpose of detecting residual disease within 12 months after completion of therapy for lymphoma or within 6 months after completion of therapy for all other malignancies”. In addition, the following note was added under surveillance of asymptomatic patients after completion of therapy for malignancy: “NOTE: Surveillance utilizing PET or PET/CT is defined as a scan performed for patients without signs or symptoms of cancer recurrence who are six (6) months or more from completion of cancer treatment or 12 months or more from completion of treatment for lymphoma”.
10/15/2015 Document updated with literature review. The following was added as an experimental, investigational and/or unproven indication for cardiac applications of positron emission tomography: Cardiac positron emission tomography scanning is considered experimental, investigational and/or unproven for quantification of myocardial blood flow in patients diagnosed with coronary artery disease. The following editorial clarification made to investigational, experimental and unproven exclusions specific to melanoma to note: PET or PET/CT is considered experimental, investigational and/or unproven for evaluation of patients with clinically localized melanoma who are candidates to undergo sentinel node biopsy.
1/1/2014 The following was added to Coverage: Sodium 18F-Fluoride (NaF-18) radiotracer for positron emission tomography (PET) bone scans is considered experimental, investigational and unproven for non-oncologic indications, including but not limited to osteomyelitis.
1/1/2012 Document updated with literature review for cardiac applications of PET. The following changes were made: 1) Requirements for cardiac PET scanning to assess myocardial perfusion defects was revised to eliminate the BMI cutoff and replace it with the phrase “in patients for whom SPECT could be reasonably expected to be suboptimal in quality on the basis of body habitus”; 2) An additional indication for PET scanning was added: “Cardiac PET scanning may be considered medically necessary for the diagnosis of cardiac sarcoidosis in patients who are unable to undergo MRI scanning. 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” ; 3) Criteria for breast cancer, prostate cancer, and melanoma were revised to only include the individual exclusions.
6/1/2011 Document updated with literature review. The following change was made: PET or PET/CT imaging for subsequent treatment strategy planning may be considered medically necessary when the initial diagnostic PET criteria were met, and the listed conditions are also met. (The list of specific diagnoses has been removed).
6/15/2010 Revised/updated document with literature review. The following changes were made: 1) New medical necessity criteria for oncologic uses of PET or PET/CT include: a) initial treatment strategy planning when criteria are met (with additional criteria and exclusions for breast cancer, melanoma, and prostate cancer); and b) subsequent treatment strategy planning for cancers of the breast, cervix, colon and rectum, esophagus, head and neck, non-small cell lung, lymphoma, melanoma, myeloma, ovary, and thyroid; c) PET or PET/CT is considered experimental, investigational and unproven for subsequent treatment strategy planning for any other tumor/cancer not listed above. (This includes, but is not limited to pancreatic cancer); d) PET or PET/CT is considered not medically necessary for patients ≥12 months after completion of therapy for lymphoma, or ≥6 months after completion of therapy for all other malignancies, unless the patient demonstrates signs, symptoms, laboratory or other objective findings suggestive of recurrence or spread of the original malignancy. 2) Positron emission mammography (PEM) was added to coverage: PEM is considered experimental, investigational and unproven for breast cancer screening, diagnosis or management. 3) The AHA/ACC Joint Statement for assessment of cardiovascular risk was added to the Description section to assist determination of intermediate risk.
10/1/2009 Revised/updated entire document
7/1/2009 Policy revised to allow coverage of PET for ovarian cancer, pancreatic cancer, small cell lung cancer, and soft tissue sarcoma.
3/1/2008 Revised/Updated Entire Document
2/1/2005 Revised/Updated Entire Document
10/16/2004 Revised/Updated Entire Document
10/1/2003 Codes Revised/Added/Deleted
8/1/2003 Revised/Updated Entire Document
5/1/2000 Codes Revised/Added/Deleted
1/1/2000 Codes Revised/Added/Deleted
9/1/1999 Codes Revised/Added/Deleted
4/1/1999 Codes Revised/Added/Deleted
5/1/1996 Codes Revised/Added/Deleted
10/1/1994 Codes Revised/Added/Deleted
10/1/1992 Codes Revised/Added/Deleted
7/1/1992 Codes Revised/Added/Deleted
1/1/1992 Codes Revised/Added/Deleted
5/1/1990 New Medical Document

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