Cardiac 123I- m IBG Imaging in Heart Failure

Abstract

Cardiac sympathetic upregulation is one of the neurohormonal compensation mechanisms that play an important role in the pathogenesis of chronic heart failure (CHF). In the past decades, cardiac ¹²³I-mIBG scintigraphy has been established as a feasible technique to evaluate the global and regional cardiac sympathetic innervation. Although cardiac ¹²³I-mIBG imaging has been studied in many cardiac and neurological diseases, it has extensively been studied in ischemic and non-ischemic CHF. Therefore, this review will focus on the role of ¹²³I-mIBG imaging in CHF. This non-invasive, widely available technique has been established to evaluate the prognosis in CHF. Standardization, especially among various combinations of gamma camera and collimator, is important for identifying appropriate thresholds for adequate risk stratification. Interestingly, in contrast to the linear relationship between ¹²³I-mIBG-derived parameters and overall prognosis, there seems to be a "bell-shape" curve for ¹²³I-mIBG-derived parameters in relation to ventricular arrhythmia or appropriate implantable cardioverter defibrillator (ICD) therapy in patients with ischemic CHF. In addition, there is a potential clinical role for cardiac ¹²³I-mIBG imaging in optimizing patient selection for implantation of expensive devices such as ICD and cardiac resynchronization therapy (CRT). Based on cardiac ¹²³I-mIBG data risk models and machine learning, models have been developed for appropriate risk assessment in CHF.

Keywords: 123I-mIBG scintigraphy; chronic heart failure; heart-to-mediastinum ratio; innervation.

Figure 1

Schematic representation of the sympathetic synapse. Norepinephrine is synthesized within neurons by an enzymatic cascade. Dihydroxyphenylalanine (DOPA) is generated from tyrosine and subsequently converted to dopamine by DOPA decarboxylase. Dopamine is transported into storage vesicles by the energy-requiring vesicular monoamine transporter (VMAT). Norepinephrine is synthesized by dopamine β-hydroxylase within these vesicles. Neuronal stimulation leads to norepinephrine release through fusion of vesicles with the neuronal membrane (exocytosis). Apart from neuronal stimulation, release is also regulated by a number of presynaptic receptor systems, including α2–adrenergic receptors, which provide negative feedback for exocytosis. Most norepinephrine undergoes re-uptake into nerve terminals by the presynaptic norepinephrine transporter (NET) and is re-stored in vesicles (following uptake by vesicular amine transporter 2 (VMAT2)) or is metabolized in cytosol dihydroxyphenylglycol (DHPG) by monoamine oxidase (MAO). (Adapted from Verschure et al. [1].

Figure 2

Example of placing a circular or elliptical region of interest (ROI) over the heart (H) and fixed rectangular mediastinal ROI placed on the upper part of the mediastinum (M) for calculating heart-to-mediastinum ratio (H/M). The same ROIs are placed on early and late images to calculate H/M and washout. The H/M outcomes are standardized to the ME-collimator condition.

Figure 3

Variations of ¹²³I-mIBG washout (WO) calculation using the myocardial count densities requiring a time decay correction factor (DCF) without (B) or with background correction (C). Calculating the DCF value by the formula of 1/0.5^(time/13) for 3.0, 3.5 or 4.0 h, the DCF are 1.17, 1.21 and 1.24, respectively.

Figure 4

Examples of late ¹²³I-mIBG CZT SPECT (D-SPECT, Spectrum Dynamics) imaging in a near-normal patient (A) and a patient with after an inferolateral myocardial infarction (B). Conventional short-axis, vertical and horizontal axis slices (left panel), and the corresponding 17-segment model polar map (right panel).

Figure 5

¹²³I-mIBG H/M and breakdown of serious events (A); death from terminal heart failure (HF), progression of HF, sudden cardiac death, and appropriate ICD therapy [67]. The right panel (B) shows machine-learning-based simulation of probability of fatal arrhythmic death. In this simulation a model was created based on patients with documented 2-year outcomes of CHF using 13 variables including age, gender, NYHA functional class, left ventricular ejection fraction and planar ¹²³I-mIBG late H/M ratio [71]. The bell-shape appearance of serious arrhythmic events as observed in clinical studies is replicated by simulation models as well.

Figure 6

A 60-year-old Japanese woman diagnosed with Takotsubo syndrome. The ¹²³I-mIBG early SPECT show a clear defect in the apical region, and the late image also showed a similar defect (figure not shown). The early and late planar H/M ratio of this patient are shown in Figure 2, showing preserved ¹²³I-mIBG uptake globally despite the severe apical defect.