Cardiac 123 I - MIBG scintigraphy – why , how and who ?

The cardiac sympathetic nervous system in health and disease Anatomically the heart, particularly the left ventricular (LV) myocardium, has dense sympathetic innervation. Postganglionic neurons originate in the thoracic, stellate and cervical ganglia of the sympathetic chain, and run alongside the coronary arteries from the base to the apex of the heart, innervating myocardium and blood vessels along the way. Sympathetic nerve stimulation causes rapid release of the neurotransmitter norepinephrine (NE) from presynaptic terminals, which activates adrenergic receptors (adrenoceptors) on the surface of adjacent cardiac myocytes (figure 1). This leads to changes in chronotropy, inotropy and lusitropy (relaxation) via G-proteincoupled intracellular mechanisms. Abnormal sympathetic function is an important component of the pathogenesis of heart failure. Increased sympathetic tone initially aids the failing cardiovascular system, raising cardiac output through an increase in heart rate and myocardial contractility. However, long-term overstimulation leads to increased peripheral vascular constriction and salt and water retention, increasing afterload and preload on the heart. There are also direct toxic effects on the myocardium, with increased risk of arrhythmias, desensitisation of adrenoceptors, and triggering of myocyte death by apoptosis. Cardiac sympathetic function can also be disrupted following myocardial infarction, with damage not only to sympathetic neurons innervating the infarcted territory itself, but also to fibres running through the infarct zone on their way to innervate more apical regions of the left ventricular myocardium. This may produce an area of viable and perfused but denervated muscle, which could act as a substrate for subsequent ventricular arrhythmias. Some studies have also demonstrated abnormal cardiac sympathetic function in the setting of advanced coronary artery disease without prior infarction. Cardiac sympathetic abnormalities have been implicated in the pathogenesis of hypertrophic cardiomyopathy. It is suggested that sympathetic overstimulation produces trophic factors that contribute to left ventricular hypertrophy, while excess NE provokes myocyte growth, fibre disarray and scarring. This theory could explain why b-blockers are beneficial in hypertrophic cardiomyopathy. Principle of cardiac I-MIBG scintigraphy Meta-iodobenzylguanidine (MIBG) is an analogue of NE with similar pharmacokinetic properties, allowing it to be used in the assessment of sympathetic function (figure 2). Following intravenous injection, MIBG is taken up into presynaptic nerve terminals via the NE transporter membrane protein, and stored in vesicles (figure 1). In contrast to NE and other endogenous catecholamines, MIBG is not metabolised by either the monoamine oxidase or catechol O-methyltransferase enzyme systems. Thus, the uptake of MIBG within the LV myocardium reflects the anatomical and physiological integrity of sympathetic nerve terminals. When labelled with the radionuclide iodine-123, the distribution of MIBG can be imaged scintigraphically with a gamma camera. This allows non-invasive evaluation of global and regional sympathetic nerve function using planar or single photon emission computed tomography (SPECT) imaging respectively. I-MIBG scintigraphy was initially used in humans for the investigation of catecholamine producing tumours of the adrenal medulla, such as phaeochromocytoma and neuroblastoma. Although shown to be feasible more than 20 years ago, cardiac I-MIBG imaging has not been widely used in clinical practice in the UK. Recently there has been a resurgence of interest, particularly in the setting of heart