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A.6.01.56
In individuals with heart failure, activation of the sympathetic nervous system is an early response to compensate for decreased myocardial function. The concentration of iodine 123 meta-iodobenzylguanidine (MIBG) over several hours after the injection of the agent is a potential marker of sympathetic neuronal activity. Iodine 123 meta-iodobenzylguanidine activity is proposed as a prognostic marker in individuals with heart failure to aid in the identification of individuals at risk of 1- and 2-year mortality. The marker could also be used to guide treatment decisions or to monitor the effectiveness of heart failure treatments.
Heart Failure
An estimated 6.7 million adults in the United States have heart failure. In 2022, heart failure was mentioned on 457,212 death certificates in the U.S. According to data in the 2022 Heart and Stroke Statistics Update, 1 in 6 patients with heart failure and reduced ejection fraction developed worsening disease within 18 months of diagnosis and these individuals were more likely to be Black, >80 years of age, and have increased comorbidity burden. Black individuals also have the highest risk of developing heart failure in the future, followed by Hispanic, White, and Chinese American individuals, reflecting disparities in the incidence of hypertension, diabetes, and socioeconomic status among these populations. Black individuals also have the highest proportion of incident heart failure not preceded by myocardial infarction (75%). Underlying causes of heart failure include coronary artery disease, hypertension, valvular disorders, and primary cardiomyopathies. These conditions reduce myocardial pump function and decrease left ventricular ejection fraction. An early mechanism to compensate for this decreased myocardial function is activation of the sympathetic nervous system. The increased sympathetic activity initially helps compensate for heart failure by increasing heart rate and myocardial contractility to maintain blood pressure and organ perfusion. However, over time, this places additional strain on the myocardium, increasing coronary perfusion requirements, which can lead to worsening of ischemic heart disease and or myocardial damage. As the ability of the heart to compensate for reduced myocardial function diminishes, clinical symptoms of heart failure develop. Another detrimental effect of heightened sympathetic activity is an increased susceptibility to potentially fatal ventricular arrhythmias.
Overactive sympathetic innervation associated with heart failure involves increased neuronal release of norepinephrine (NE), the main neurotransmitter of the cardiac sympathetic nervous system. In response to sympathetic stimulation, vesicles containing NE are released into the neuronal synaptic cleft. The released NE binds to post-synaptic beta-1, beta-2, and alpha receptors, enhances adenyl cyclase activity, and brings about the desired cardiac stimulatory effects. Norepinephrine is then taken back into the presynaptic space for storage or catabolic disposal, terminating the synaptic response by the uptake-1 pathway. The increased release of NE is usually accompanied by decreased NE reuptake, thereby further increasing circulating NE levels.
Diagnostic Imaging
Guanethidine is a false neurotransmitter that is an analogue of NE; it is also taken up by the uptake-1 pathway. Iodine 123 meta-iodobenzylguanidine (¹²³I-MIBG or MIBG) is chemically-modified guanethidine labeled with radioactive iodine. Iodine 123 meta-iodobenzylguanidine moves into the synaptic cleft and then is taken up and stored in the presynaptic nerve space in a manner similar to NE. However, unlike NE, MIBG is not catabolized and thus concentrates in myocardial sympathetic nerve endings. This concentrated MIBG can be imaged with a conventional gamma camera. The concentration of MIBG over several hours after injection is thus a reflection of sympathetic neuronal activity, which in turn may correlate with the severity of heart failure.
Iodine 123 meta-iodobenzylguanidine myocardial imaging has been in use in Europe and Japan, and standardized procedures for imaging have been proposed by European organizations. Administration of MIBG is recommended by slow (1 to 2 minute) injection. Planar images of the thorax are acquired 15 minutes (early image) and 4 hours (late image) after injection. In addition, optional single-photon emission computed tomography (SPECT) can be performed following the early and late planar images. Iodine 123 meta-iodobenzylguanidine uptake is semi-quantified by determining the average count per pixel in regions of interest drawn over the heart and the upper mediastinum in the planar anterior view. There is no single universally used myocardial MIBG index. The most commonly used myocardial MIBG indices are the early heart to mediastinum (H/M) ratio, late H/M ratio, and the myocardial MIBG washout rate. The H/M ratio is calculated by taking the average count per pixel in the myocardium divided by the average count per pixel in the mediastinum. The myocardial washout rate is expressed as the rate of decrease in myocardial counts over time between early and late imaging (normalized to mediastinal activity).
Iodine 123 meta-iodobenzylguanidine activity is proposed as a prognostic marker in patients with heart failure, to be used in conjunction with established markers or prognostic models to identify heart failure patients at increased risk of short-term mortality. Iodine 123 meta-iodobenzylguanidine activity could also be used to guide treatment decisions or to monitor the effectiveness of heart failure treatments.
In 2008, AdreView® (lobenguane I 123) Injection (GE Healthcare) was approved by the U.S. Food and Drug Administration (FDA) new drug application process (22-290) for the detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests.
In 2013, the FDA approved a supplemental new drug application (22-290/S-001) for AdreView and expanded the labeled indication to include scintigraphic assessment of sympathetic innervation of the myocardium by measurement of the heart to mediastinum (H/M) ratio of radioactivity uptake in patients with New York Heart Association (NYHA) class II or class III heart failure and left ventricular ejection fraction (LVEF) <35%.
Related policies -
Myocardial sympathetic innervation imaging with iodine 123 meta-iodobenzylguanidine (MIBG) is considered investigational for use in individuals with heart failure.
Federal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
04/01/2014: Approved by Medical Policy Advisory Committee.
08/06/2014: Policy reviewed; description updated. Policy statement unchanged.
08/04/2015: Code Reference section updated for ICD-10.
10/20/2015: Policy reviewed. Investigative definition updated in policy guidelines section.
05/31/2016: Policy number A.6.01.56 added.
10/14/2016: Policy reviewed; no changes.
10/18/2017: Policy description updated regarding FDA approvals and indications. Policy statement unchanged.
10/09/2018: Policy reviewed; no changes.
10/31/2019: Policy reviewed; no changes.
10/15/2020: Policy description updated. Policy statement unchanged.
01/10/2022: Policy description updated regarding patients with heart failure in the United States. Policy statement unchanged.
12/02/2022: Policy description updated regarding new data for heart failure. Policy statement updated to change "patients" to "individuals."
10/12/2023: Policy reviewed; no changes.
11/20/2024: Policy title and medical policy language revised to change "patients" to "individuals." Policy description updated regarding new heart failure data. Policy statement updated with minor revision to state that myocardial sympathetic innervation imaging with iodine 123 meta-iodobenzylguanidine (MIBG) is considered investigational for use in individuals with heart failure.
Blue Cross and Blue Shield Association Policy # 6.01.56
This may not be a comprehensive list of procedure codes applicable to this policy.
Code Number | Description |
CPT-4 | |
0331T | Myocardial sympathetic innervation imaging, planar qualitative and quantitative assessment;; |
0332T | Myocardial sympathetic innervation imaging, planar qualitative and quantitative assessment; with tomographic SPECT |
HCPCS | |
A9582 | Iodine I-123 iobenguane, diagnostic, per study dose, up to 15 millicuries |
ICD-10 Procedure | |
ICD-10 Diagnosis |
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