Guest Bloggers:The metaiodobenzylguanidine (MIBG) is a noradrenaline analogue (1-3) that uses the same mechanism of noradrenaline uptake and storage in presynaptic vesicles.(2,4-7) It also has no pharmacological action and has low affinity for postsynaptic receptors. This provides its retention and localization in the sympathetic nerve endings of the myocardium in sufficient concentration, allowing the characterization of cardiac sympathetic function and the integrity of the adrenergic neurons.(2,7) Positron emission tomography imaging has also been used for assessment of cardiac innervation with the use of 11C hydroxyephedrine.(8)
Gabriel Blacher Grossman, MD, PhD, FASNC
Rafael W. Lopes, MD, PhD, FASNC
MIBG is labeled with iodine-123 (123I) to take advantage of its relatively low dosimetry and suitable energy for imaging, allowing planar and tomographic images (SPECT: single photon emission computed tomography) to be obtained. Through these images, it is possible to evaluate the cardiac uptake of MIBG and its distribution. Visually and semi-quantitatively, two key parameters are analyzed: heart-mediastinum ratio (H/MR) and myocardial washout rate (WR). SPECT images can be used to compare patterns of innervation and perfusion, and to obtain prognostic information.(1-3,6-7) Table 1 summarizes the protocol of 123I-MIBG imaging.
The literature presents different normal values for these criteria(3,9), and there is still no standardization. However, a H/MR ranging from 1.9 to 2.8 is usually considered normal, with an average of 2.2 ± 0.3 (in late images)(2,7), with a value lower than 1.6 (2 standard deviations below the mean) being considered to be abnormal and correlating with patients at increased cardiovascular risk.(10) For WR, values of 20% ± 10% are considered normal, being higher in patients with high cardiovascular risk of hard events.(3,11) See Figure 1.
Figure 1. H/MR: Heart/Mediastinum ratio. Low risk for arrythmias or sudden death H/MR ≥1.6. High risk for arrythmias or sudden death H/MR < 1.6. (Figure courtesy Drs. Ronaldo Leão Lima and Adriana Xavier de Brito.)
MIBG, Heart Failure and Sudden Cardiac Death
MIBG is a powerful risk stratification tool in patients with heart failure (HF).(1,3) Cardiac sympathetic imaging with 123I-MIBG is an important method to evaluate the risk of patients developing arrhythmias or sudden cardiac death (SCD).(12)
Multiple studies have shown that the evaluation of cardiac sympathetic nerve activity using 123I-MIBG imaging, especially the H/MR, can differentiate high-risk from low-risk patients, regardless of left ventricular ejection fraction (LVEF), brain natriuretic peptide and New York Heart Association (NYHA) clinical conditions.(1-3,6-7) The AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) evaluated 961 patients with HF, NYHA functional class II/III, LVEF <= 35% and who were on optimal medical therapy. Events (HF progression, arrhythmic events and cardiac death) at 2 years were compared and occurred in 15% of patients with a H/MR value >= 1,6 and in 37% in those with a H/MR <1,6.(10)
Despite the evidence that H/MR is a significant risk predictor for arrhythmic events and SCD, especially in patients with heart failure, there is no published data indicating improvement in outcomes in HF patients using this method to make decisions. Therefore, more data is necessary before incorporating MIBG scintigraphy in HF guidelines.
MIBG and Takotsubo Syndrome
Takotsubo cardiomyopathy (TTC; also called neurogenic cardiomyopathy or broken heart syndrome) is a reversible cardiac syndrome, usually precipitated by a stressful event and characterized by transient left ventricular dysfunction, electrocardiographic changes similar to those of acute myocardial infarction and minimal changes in cardiac enzymes, in the absence of obstructive coronary artery disease.(8)
The evaluation of TTC by 123I-MIBG scintigraphy demonstrates a defect in MIBG uptake usually at the apex, with normal or mildly abnormal myocardial perfusion observed by perfusion scintigraphy with sestamibi-99mTc (see Figure 2). Semiquantitative analysis also demonstrates reduction of H/MR and increase in MIBG washout. Abnormalities in 123I-MIBG scintigraphy can be detected hours to days after ischemic insult because sympathetic nerve cells take longer to recover than myocytes after an ischemic event. Due to the probable pathophysiology of TTC and the high sensitivity of sympathetic nervous cells to the ischemic insult and the delay in its recovery, it may be useful in the recognition of Takotsubo syndrome.(8) However, there is a clear need for greater evidence to confirm the clinical usefulness of 123I-MIBG imaging in this scenario.
Figure 2. Top: Tc-99m-sesamibi images demonstrate normal perfusion at rest. Bottom: MIBG images demonstrate a defect in radiotracer uptake at the apex and the inferior wall. (From personal archive.)
MIBG and Cardiac Amyloidosis
Patients with cardiac amyloidosis are prone to have autonomic dysfunction. 123I-MIBG scintigraphy is not able to discriminate between cardiac amyloidosis subtypes nor differentiate cardiac amyloidosis from other forms of cardiomyopathy. Several studies demonstrated abnormal H/MRs in patients with cardiac amyloidosis.(13)
MIBG and Cardiotoxicity
Alternative noninvasive methods for early diagnosis of cardiotoxicity have emerged. The assessment of cardiac sympathetic function using 123I-MIBG scanning has arisen as a promising tool since adrenergic damage appears to precede structural cardiac damage. Small studies demonstrated changes in the parameters of 123I-MIBG that seem to occur in parallel with the deterioration of LVEF, with a decrease in the H/MR occurring earlier in some studies when LVEF is still preserved.(14)
The diagnostic and prognostic potential of neuronal imaging throughout nuclear cardiology is huge. 123I-MIBG imaging is currently the most commonly used technique based on several published studies. Its role in the risk stratification of HF and in the recognition of Takotsubo syndrome is well known, but the importance of this information needs more data to confirm the clinical usefulness in these scenarios. Emerging applications include evaluation of patients with cardiac amyloidosis and for potential drug cardiotoxicity.
Keywords: Cardiotoxicity, 123I-MIBG scintigraphy.
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Gabriel Blacher Grossman, MD, PhD, FASNC, is a cardiologist and nuclear medicine physician and the director of nuclear medicine at Moinhos de Vento Hospital in Porto Alegre, Brazil. He is a member of ASNC's Board of Directors and the membership and social media committees. Twitter handle: @Ggrossman11.
Rafael W. Lopes, MD, PhD, FASNC, is a cardiologist and nuclear medicine physician and the director of nuclear cardiology at Hospital do Coração-HCOR in São Paulo, Brazil. He is a member of ASNC's membership committee and International Advisory Panel. Twitter handle: @rafaelnuclear.