CAM 60156

Myocardial Sympathetic Innervation Imaging in Patients with Heart Failure

Category:Radiology   Last Reviewed:August 2018
Department(s):Medical Affairs   Next Review:August 2019
Original Date:August 2013    

Description
In patients with heart failure, activation of the sympathetic nervous system is an early mechanism to compensate for decreased myocardial function. The concentration of iodine 123 meta-iodobenzylguanidine (MIBG) over several hours after injection of the agent is a potential marker of sympathetic neuronal activity and may correlate with the severity of heart failure. MIBG activity is proposed as a prognostic marker in patients with heart failure to aid in the identification of patients at risk of 1- and 2-year mortality. The marker could also potentially be used to guide treatment decisions or to monitor the effectiveness of heart failure treatments.

For individuals with heart failure who receive imaging with MIBG for prognosis, the evidence includes numerous studies that MBIG cardiac imaging findings predict outcomes in patients with heart failure. Relevant outcomes are overall survival, disease-specific survival, functional outcomes, health status measures, quality of life, hospitalizations, and medication use. While the available studies vary in their patient inclusion criteria and methods for analyzing MIBG parameters, the highest quality studies demonstrate a significant association between MIBG imaging results and adverse cardiac events, including cardiac death. Moreover, MIGB findings have been shown to improve the ability of the Seattle Heart Failure Model and other risk models to predict mortality. However, there is no direct published evidence on the clinical utility of MIBG (i.e., whether findings of the test would lead to patient management changes that improve health outcomes) and no clear chain of indirect evidence of clinical utility. Management changes made as a result of MIBG imaging are uncertain, and it is not possible to determine whether management changes based on MIBG results lead to superior outcomes compared with management without MIBG imaging. The evidence is insufficient to determine the effects of the technology on health outcomes.

Background
An estimated 5.7 million adults in the United States have heart failure, and heart failure is the main cause of death for approximately 55,000 Americans each year.1 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), which is 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 postsynaptic β1, β2 and αreceptors, enhances adenyl cyclase activity and brings about the desired cardiac stimulatory effects. NE is then taken back into the presynaptic space for storage or catabolic disposal that terminates 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. 

Guanethidine is a false neurotransmitter that is an analog of NE. It is also taken up by the uptake-1 pathway.1,2,3 Iodine meta-iodobenzylguanidine (1,2,3I-MIBG or MIBG) is guanethidine that is chemically modified and labeled with radioactive iodine. MIBG moves into the synaptic cleft and then is taken up and stored in the presynaptic nerve space in a manner that is 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.2 The concentration of MIBG over several hours after injection of the agent is thus a reflection of sympathetic neuronal activity, which in turn may correlate with the severity of heart failure. 

MIBG myocardial imaging has been in use in Europe and Japan, and standardized procedures for imaging have been proposed by European organizations.3 Administration of MIBG is recommended by slow (1-2 minutes) 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 imaging can be performed following the early and late planar images. MIBG uptake is semiquantified 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). 

MIBG 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. MIBG activity could also potentially be used to guide treatment decisions or to monitor the effectiveness of heart failure treatments.

Regulatory Status
In September 2008, AdreView® (Iobenguane I 123) Injection (GE Healthcare) was approved by the Food and Drug Administration (FDA) the new drug application (NDA) process (NDA 22-290) for the detection of primary or metastatic pheochromocytoma or neuroblastoma as an adjunct to other diagnostic tests.4

In March 2013, the FDA approved a supplemental application (NDA 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%.5

Related Policies
None

Policy
Myocardial sympathetic innervation imaging with 123Iodine meta-iodobenzylguanidine (MIBG) is considered INVESTIGATIONAL for patients with heart failure.

Policy Guidelines
Effective July 1, 2013, there are specific CPT category III codes for this imaging:

0331T: Myocardial sympathetic innervations imaging; planar qualitative and quantitative assessment
0332T: with tomographic SPECT
There is a specific HCPCS code for AdreView:

A9582: Iodine I-123 iobenguane, diagnostic, per study dose, up to 15 millicuries

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

The U.S. Food and Drug Administration (FDA)‒approved indication for the scintigraphic imaging agent iodine 123 meta-iodobenzylguanidine (MIBG) in heart failure patients is to measure the heart to mediastinum (H/M) ratio, which can be used to predict the risk of 1- and 2-year mortality. While the H/M ratio can be used as a dichotomous or a continuous variable, the FDA-approved indication is a dichotomous variable with an in H/M cutoff of 1.6. A ratio less than 1.6 indicates higher risk, and a ratio of 1.6 or greater indicates lower risk.6 Thus, evaluation of this technology involves first searching for evidence that an H/M ratio of at least 1.6 is statistically associated with mortality in heart failure patients. Then, to demonstrate that this technology improves health outcomes, direct or indirect evidence is needed that managing patients with MIBG imaging impacts treatment decisions in a way that will lead to improved outcomes compared with managing patients without MIBG imaging.

HEART FAILURE
Clinical Validity
The first step in evaluating MIBG is evaluating its prognostic accuracy, specifically, whether an H/M ratio of less than 1.6 is associated with a higher risk of heart failure mortality.

Systematic Reviews
A 2008 systematic review by Verberne et al selected studies that reported survival in patients with heart failure stratified by MIBG myocardial parameters (early H/M, late H/M, and/or myocardial washout). 

Eighteen studies met the eligibility criteria. Thirteen studies were prospective, and all but 1 had at least 3 months of follow-up. Sample sizes ranged from 37 to 205 patients; 5 studies included more than 100 patients. Patient populations varied across studies. Some studies included the whole heart failure spectrum (i.e., New York Heart Association [NYHA] functional status class I-IV) and others focused on a narrower range of functional status. Fourteen studies included patients with depressed left ventricular ejection fraction (LVEF; <40%). Acquisition of early H/M ratio was performed at 15 to 20 minutes in 9 studies and ranged from 30 to 60 minutes in the other 6 studies. Seventeen studies acquired late H/M ratio at 240 minutes after injection. Reviewers evaluated methodologic quality using a tool they developed to rate each study; the scoring range was 0 to 9. The median quality score of the included studies was 6; 2 studies scored 9.

In reviewers’ initial calculations, the pooled hazard ratio (HR) for death and late H/M ratio and for a cardiac event and late H/M ratio showed significant heterogeneity among studies, and therefore pooled results were not presented for the entire body of studies. Reviewers eliminated statistical heterogeneity by selecting the highest quality studies (i.e., top 5th in terms of quality score, n=3 studies). When findings from these 3 highest quality studies were pooled, there was a statistically significant effect of MIGB on cardiac events (HR=1.98; 95% confidence interval [CI], 1.57 to 2.50). However, when findings from the 2 highest quality studies reporting the outcome of cardiac death were pooled, there was no statistically significant effect of MIBG on this outcome (HR=1.82; 95% CI, 0.80 to 4.12). Reviewers did not pool findings on the prognostic value of early H/M or myocardial washout due to failure to identify a subset of studies without heterogeneity.

Prospective Studies
ADMIRE-HF Study
In 2010, Jacobson et al published data from 2 prospective, multicenter industry-sponsored studies, together known as the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF).8 This study was the primary evidence used by the Food and Drug Administration (FDA) to grant approval for AdreView. The analysis presented the combined primary efficacy results of the 2 studies. The study included patients with NYHA functional class II or III heart failure and LVEF of 35% or lower, which are the clinical parameters specified by FDA documents as the appropriate criteria for use of AdreView in heart failure patients. In addition, patients had to be treated with optimum pharmacotherapy. Major exclusion criteria were serum creatinine above 3.0 mg/dL, functioning ventricular pacemaker and cardiac revascularization, myocardial infarction, or implantable cardioverter defibrillator implantation within the past 30 days.

Patients received an injection of MIBG and then underwent planar and single-photon emission computer tomography (SPECT) imaging of the thorax at 15 minutes after injection (early) and at 3 hours and 50 minutes after injection (late). The H/M ratio, on a scale from 0 to 4, was determined from both the early and late images. Patients then received standard clinical care and were followed for 2 years. The primary analysis evaluated the association between time to first cardiac event occurrence and the late H/M ratio categorized as under 1.6 or 1.6 and higher. The authors also evaluated the association between time to first cardiac event occurrence and late H/M ratio as a continuous variable. The composite outcome of cardiac events was defined as the occurrence of either (1) heart failure progression (i.e., increase of ≥1 NYHA functional class); (2) potentially life-threatening arrhythmic event (i.e., spontaneous ventricular tachyarrhythmia for >30 seconds, resuscitated cardiac arrest, or appropriate discharge of implantable cardiac defibrillator); or (3) cardiac death.

A total of 985 patients underwent MIBG imaging (435 in the first study, 532 in the second study) and 961 (98%) patients were available for analysis. There were 760 (79%) patients with an H/M ratio less than 1.60 and 201 (21%) patients with an H/M ratio at least 1.60. Patients were followed for a median of 17 months (range, 2 days to 30 months). Cardiac events occurred in 237 (25%) of 961 patients. The mean late H/M ratio (standard deviation [SD]) was 1.39 (0.18) in the group of patients with events and 1.46 (0.21) in the group of patients without events. The risk of cardiac events was significantly lower for patients with an H/M at least 1.6 compared with those with an H/M ratio less than 1.6 (HR=0.40; 97.5% CI, 0.25 to 0.64; p<0.001). In addition, there was a statistically significant association between the cardiac event rate and H/M ratio as a continuous variable, with lower event rates on patients with higher H/M ratios (HR=0.22; 95% CI, 0.10 to 0.47; p<0.001). The estimate of 2-year all-cause mortality was 16.1% for patients with an H/M less than 1.60 and 3.0% for patients with an H/M ratio at least 1.60 (p<0.001). The authors also compared H/M ratio with other prognostic markers. In a multivariate model including the H/M ratio, b-type natriuretic peptide, LVEF, and NYHA functional class, all 4 markers were independently associated with time to cardiac events.

In 2012, Ketchum et al published an analysis incorporating MIGB imaging findings into the Seattle Heart Failure Model (SHFM) using survival data from the 961 patients included in the primary efficacy analysis of the ADMIRE-HF study.9 The late H/M ratio from MIBG imaging was divided into 5 categories: less than 1.2, 1.2 to 1.39, 1.40 to 1.59, 1.6 to 1.79, and at least 1.8. (Note that this differs from the dichotomous late H/M variable used in the main ADMIRE-HF analysis.) In a Cox proportional hazards model, SHFM and H/M were both independent predictors of overall survival. There was an 82.1% increase in risk for a 1 SD change in the SHFM (p<0.001) and a 60.3% increase in risk for a 1 SD change in the late H/M ratio (p<0.001). For the outcome cardiac mortality, each SD increase in SHFM was associated with an 86.1% increase in risk (p<0.001), and each SD increase in the late H/M ratio was associated with a 57.9% increase in risk (p=0.002). In an area under the curve (AUC) analysis, the addition of H/M to the SHFM significantly improved the prediction of all-cause mortality compared with the SHFM alone. When H/M was added to the SHFM, the AUC increased by 0.039 (p=0.026) for 1-year mortality, and the AUC increased by 0.028 (p<0.05) for 2-year mortality.

In 2013, Sood et al published a subgroup analysis of the ADMIRE-HF study to evaluate whether resting perfusion defects on myocardial perfusion imaging (MPI) with SPECT, representing scarring or fibrosis, added to risk stratification beyond the H/M ratio in the prediction of ventricular arrhythmias in ischemic and nonischemic cardiomyopathy patients.10 In 317 nonischemic cardiomyopathy patients, MPI-SPECT score (summed rest score, >8) had incremental predictive value for ventricular arrhythmias for those with a low H/M ratio. Among the 612 patients with ischemic cardiomyopathy, MPI-SPECT results did not have incremental predictive value.

In 2014, Al Badarin et al published another subgroup analysis of the ADMIRE-HF study to evaluate whether the addition of MIBG scintigraphy to conventional markers of arrhythmic risk had incremental predictive value for arrhythmic events in patients with heart failure.11 This analysis included 778 patients from ADMIRE-HF with an LVEF less than 35% and NYHA class II or III heart failure symptoms who did not have an implantable cardioverter defibrillator (ICD) at the time of enrollment. Of these, 6.9% experienced the primary end point of an arrhythmic event, which was a composite of sudden cardiac death, appropriate ICD therapy, resuscitated cardiac arrest, or sustained ventricular tachycardia. An H/M ratio less than 1.6 was significantly associated with risk of arrhythmic events (HR=3.48; 95% CI, 1.52 to 8; p=0.02). Other predictors of arrhythmic events were LVEF less than 25% and systolic blood pressure (SBP) less than 120 mm Hg. The authors derived a risk score, incorporating H/M ratio, SBP, and LVEF. Risk scores ranged from -3 to 20, with higher scores associated with increased risk of arrhythmic events. Stratified by tertiles, patients with low (<4), intermediate (4-15), and high (>15) risk scores had significantly different arrhythmic event rates (2%, 10%, 16%, respectively; p<0.001). The integrated discrimination improvement (IDI) by adding MIBG imaging results to the risk model, which included SBP and LVEF, was 0.45 (absolute IDI=0.01; 95% CI, 0.001 to 0.014), which demonstrated a 45% improvement in discriminatory ability with the addition of MIBG results.

Also in 2014, Jain et al evaluated the incremental predictive value of adding MIBG imaging to 4 published heart failure risk models using data from ADMIRE-HF.12 The 4 risk models varied in the patient populations from which they were derived and in their predictor variables. In the ADMIRE-HF population, the 4 models had modest discrimination for identifying patients at risk of experiencing the composite primary end point of heart failure progression necessitating hospital admission, life-threatening arrhythmia, or cardiac death (C statistic range, 0.611-0.652). When the H/M ratio was added to the risk prediction models, the IDI had an absolute improvement of 2.1% to 3.0% in each model, representing a relative improvement in predictive utility ranging from 33% to 59%.

In 2015, Narula et al reported on the ADMIRE-HF extension study (ADMIRE-HFX), which extended follow-up to a median of 24 months and focused specifically on the predictive value of MIBG imaging for mortality prediction.13 The primary end point for this extension study was all-cause mortality, which was analyzed using 2 coprimary analysis methods, proportional hazards, and logistic regression. In both multivariate Cox proportional hazards analysis and multivariate logistic regression analysis with receiver operating characteristic curve comparisons, the H/M ratio was a significant additional predictor for all-cause mortality (hazard ratio [HR], 0.08; p<0.001; odds ratio, 0.07; 95% CI, 0.20 to 0.238, respectively).

Other Prospective Studies
For patients with heart failure without reduced LVEF (i.e., LVEF of at least 50%), several prospective studies have found the MIBG is an independent predictor of cardiac outcomes.14-18 For example, a 2012 prospective single-center study by Doi et al evaluated the prognostic value of MIBG activity assessment in 178 heart failure patients without reduced LVEF.15 Eligibility for the trial included symptomatic heart failure and LVEF more than 50%. Mean LVEF in the sample was 64.5%. Cardiac planar and tomographic MIBG images were obtained 15 to 30 minutes (early) and 4 hours (late) after the agent was injected. MIBG activity was quantified as the H/M ratio by an experienced technician blinded to clinical data. Patients were followed for a mean of 80 months (minimum, 3 months). The primary end points were cardiac events consisting of death, sudden cardiac death, pump failure, or rehospitalization due to the progression of heart failure. During follow-up, cardiac events were documented in 34 (19%) of 178 patients. Events included 7 deaths due to pump failure, 2 sudden deaths, and 25 readmissions due to heart failure progression. There were significantly lower early and late MIBG levels in patients who experienced cardiac events compared with those without events. This study evaluated MIBG activity as a continuous variable; it did not use a cutoff (e.g., an H/M ratio of at least 1.60), as was used to indicate decreased risk in the ADMIRE-HF study.8 The mean (SD) early H/M ratio level was 1.86 (0.38) in the group with cardiac events and 2.00 (0.31) in the group without cardiac events. The mean (SD) late H/M ratio was 1.64 (0.35) in the group with and 1.89 (0.33) in the group without cardiac events. In a multivariate analysis, use of diuretics, late atrial diameter, and late H/M ratio were all independent predictors of cardiac events.

In 2013, Nakata et al published results of a pooled patient-level analysis of 6 prospective heart failure studies from Japan in which cardiac MIBG imaging was used.19 The 6 studies initially included 1,360 patients, but 38 patients were excluded (32 due to loss to follow-up, 6 due to follow-up <1 year) for the present analysis. The H/M ratio and the washout rate of MIBG activity were the primary cardiac sympathetic innervation markers. In a multivariate Cox proportional hazards model, the late H/M ratio was significantly associated with the primary outcome of all-cause mortality (p<0.001). The addition of the H/M ratio to a model of cardiac risk based on clinical information led to a net reclassification improvement of 0.175 (p<0.001).

In 2014, Verschure et al published results of an individual patient data meta-analysis to assess which heart failure-related end point had the strongest associated with MIBG results.20 The meta-analysis included 636 patients with congestive heart failure from 6 studies from the United States and Europe. Inclusion criteria were studies reporting survival in patients with heart failure stratified by H/M ratio, which yielded 8 studies, 6six of which were willing to share individual patient data. Over a mean follow-up of 36.9 months, 159 patients had 172 events: 83 deaths (67 of which were cardiac), 33 arrhythmic events, and 56 cardiac transplantations. In univariate analysis, the H/M ratio was significantly associated with all cardiac-related outcomes, but the lowest hazard ratios were associated with the composite end point of any event (HR=0.30; 95% CI, 0.19 to 0.46), all-cause mortality (HR=0.29; 95% CI, 0.16 to 0.53), and cardiac mortality (HR=0.28; 95% CI, 0.14 to 0.55).

Section Summary: Clinical Validity
The available evidence has demonstrated that MIBG imaging is a predictor of future cardiac events and mortality in patients with heart failure. Numerous prospective studies have evaluated this question, and a systematic review that pooled the highest quality studies estimated that cardiac events were approximately 2 times more frequent for patients with a lower MIBG ratio than for those with a higher ratio. The primary study on which FDA approval was based reported that a low MIBG ratio was associated with a substantially higher mortality rate at 2 years. Data from this same study reported that addition of the MIBG score to a known prognostic index (the SHFM), resulted in improved predictive accuracy. 

Clinical Utility
As noted above, numerus prospective studies have indicated the MIBG imaging is associated as a prognostic marker with heart failure mortality. No studies were identified that evaluated the impact of cardiac sympathetic innervation assessed by MIBG on treatment decisions for heart failure or that evaluated whether managing heart failure patients with this test (vs managing patients without the test) leads to patient management decisions that improve health outcomes.

A systematic review by Treglia et al (2013) included 33 studies, primarily performed in Europe and Japan, that compared MIBG imaging results in patients with heart failure before and after receiving medication treatment.21 Reviewers provided brief descriptions of the findings of individual studies; they did not pool study results. Studies addressed different classes of medications (e.g., β-blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers) and different MIBG parameters used. The reviewers did not report the number of studies statistically significant findings but described a number of studies that found significant associations between medication treatment and changes in one or more MIBG parameters. They also described some studies that found significant associations between changes in one or more MIBG parameters and cardiac outcomes in patients receiving medication treatment. However, none of the studies used MIGB imaging results to guide medication treatment choices or compared management strategies that did and did not include MIBG imaging.

Management changes that might be made as a result of MIBG myocardial imaging are uncertain. It is possible that medication therapy could be intensified based on MIBG scanning that indicated a poor prognosis. However, the evidence is lacking that such a management change would result in improved outcomes. It is also possible that medications that block sympathetic overactivity (e.g., β-blockers or angiotensin-converting enzyme inhibitors) could be adjusted to achieve an optimal H/M ratio. It is also not known whether such medication adjustments made as a result of MIBG imaging would lead to improvements in health outcomes.

Klein et al (2015) reported on the results of a pilot study that used MIBG imaging to map substrates for ventricular tachycardia ablation,22 but the use of MIBG imaging for this purpose is still in preliminary investigations.  

Section Summary: Clinical Utility
The evidence does not support a finding that MIBG imaging can be used to direct management in patients with heart failure. Numerous studies have correlated medication changes with changes in MIBG imaging. However, these studies do not provide evidence on the type of management changes that might follow from MIBG imaging. Further studies are needed to determine the impact of MIBG imaging on health outcomes. The preferred study design to evaluate clinical utility is a randomized controlled trial comparing health outcomes in a group of heart failure patients managed using MIBG activity assessment with a group of patients managed not using MIBG activity assessment. Well-controlled prospective studies that examine clinicians’ treatment decisions based on MIBG findings compared with treatment decisions made without MIBG findings may also inform whether MIBG imaging can improve outcomes in patients with heart failure.

SUMMARY OF EVIDENCE
For individuals with heart failure who receive imaging with MIBG for prognosis, the evidence includes numerous studies that MBIG cardiac imaging findings predict outcomes in patients with heart failure. Relevant outcomes are overall survival, disease-specific survival, functional outcomes, health status measures, quality of life, hospitalizations, and medication use. While the available studies vary in their patient inclusion criteria and methods for analyzing MIBG parameters, the highest quality studies have demonstrated a significant association between MIBG imaging results and adverse cardiac events, including cardiac death. Moreover, MIGB findings have been shown to improve the ability of the Seattle Heart Failure Model and other risk models to predict mortality. However, there is no direct published evidence on the clinical utility of MIBG (i.e., whether findings of the test would lead to patient management changes that improve health outcomes) and no chain of evidence of clinical utility. Management changes made as a result of MIBG imaging are uncertain, and it is not possible to determine whether management changes based on MIBG results lead to improved health outcomes compared with management without MIBG imaging. The evidence is insufficient to determine the effects of the technology on health outcomes. 

PRACTICE GUIDELINES AND POSITION STATEMENTS
National Heart, Lung, and Blood Institute
In 2011, the National Heart, Lung, and Blood Institute published a report on the translation of cardiovascular molecular imaging.23 In regard to heart imaging with meta-iodobenzylguanidine (MIBG), the report cited the ADMIRE-HF trial,8 and stated that additional clinical trials would be needed to determine the efficacy of heart failure management strategies using MIBG compared with usual care without MIBG imaging.  

American College of Cardiology Foundation and the American Heart Association
In 2013, the American College of Cardiology Foundation and the American Heart Association published updated joint guidelines on the management of heart failure.24 These guidelines included recommendations on the use of noninvasive cardiac imaging in the management of heart failure but did not address the use of MIBG imaging in heart failure management.  

U.S. PREVENTIVE SERVICES TASK FORCE RECOMMENDATIONS
Not applicable. 

ONGOING AND UNPUBLISHED CLINICAL TRIALS
Some currently unpublished trials that might influence this review are listed in Table 1.

Table 1. Summary of Key Trials

NCT No.

Trial Name

Planned Enrollment

Completion Date

Ongoing

NCT02656329a

International Study to Determine if AdreView Heart Function Scan Can be Used to Identify Patients With Mild or Moderate Heart Failure (HF) That Benefit From Implanted Medical Device (ADMIRE-ICD)

2,216

Aug 2019

NCT: national clinical trial.
a  Denotes industry-sponsored or cosponsored trial.

References

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  18. Scala O, Paolillo S, Formisano R, et al. Sleep-disordered breathing, impaired cardiac adrenergic innervation and prognosis in heart failure. Heart. Jun 23 2016;102(22):1813-1819. PMID 27340199
  19. Nakata T, Nakajima K, Yamashina S, et al. A pooled analysis of multicenter cohort studies of (123)I-mIBG imaging of sympathetic innervation for assessment of long-term prognosis in heart failure. JACC Cardiovasc Imaging. Jul 2013;6(7):772-784. PMID 23845574
  20. Verschure DO, Veltman CE, Manrique A, et al. For what endpoint does myocardial 123I-MIBG scintigraphy have the greatest prognostic value in patients with chronic heart failure? Results of a pooled individual patient data meta-analysis.Eur Heart J Cardiovasc Imaging. Sep 2014;15(9):996-1003. PMID 24686260
  21. Treglia G, Stefanelli A, Bruno I, et al. Clinical usefulness of myocardial innervation imaging using Iodine-123-meta-iodobenzylguanidine scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with heart failure: an overview. Eur Rev Med Pharmacol Sci. Jan 2013;17(1):56-68. PMID 23329524
  22. Klein T, Abdulghani M, Smith M, et al. Three-dimensional 123I-meta-iodobenzylguanidine cardiac innervation maps to assess substrate and successful ablation sites for ventricular tachycardia: feasibility study for a novel paradigm of innervation imaging. Circ Arrhythm Electrophysiol. Jun 2015;8(3):583-591. PMID 25713216
  23. Buxton DB, Antman M, Danthi N, et al. Report of the National Heart, Lung, and Blood Institute working group on the translation of cardiovascular molecular imaging. Circulation. May 17 2011;123(19):2157-2163. PMID 21576680
  24. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. Oct 15 2013;128(16):1810-1852. PMID 23741057

Coding Section

Codes Number Description
CPT 0331T

Myocardial sympathetic innervations imaging, planar qualitative and quantitative assessment;

  0332T

; with tomographic SPECT

HCPCS

A9582

Iodine I-123 iobenguane, diagnostic, per study dose, up to 15 millicuries

ICD-9-CM Diagnosis

 

Investigational for relevant diagnoses

 

428.0-428.9

Heart failure code range

ICD-10-CM (effective 10/01/15)

 

Investigational for relevant diagnoses

 

I50.1-I50.9

Heart failure code range

ICD-10-PCS (effective 10/01/15)

 

ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this imaging.

Type of Service

   

Place of Service

   

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.  

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2014 Forward     

08/21/2018 

 Annual review, no change to policy statement. Updating regulatory status, rationale and references.

08/10/2017 

Annual review, no changes made to policy intent. Updating description, rationale and references. 

08/02/2016 

Annual review, no change to policy intent. 

08/20/2015 

Annual review, no change to policy intent. Updated background, description, rationale and references. Added guidelines and coding. 

08/04/2014

Annual review. Added related policies. Updated rationale and references. No change to policy intent


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