Cardiac sympathetic activity in chronic heart failure: cardiac 123I-mIBG scintigraphy to improve patient selection for ICD implantation

Abstract

Heart failure is a life-threatening disease with a growing incidence in the Netherlands. This growing incidence is related to increased life expectancy, improvement of survival after myocardial infarction and better treatment options for heart failure. As a consequence, the costs related to heart failure care will increase. Despite huge improvements in treatment, the prognosis remains unfavourable with high one-year mortality rates. The introduction of implantable devices such as implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) has improved the overall survival of patients with chronic heart failure. However, after ICD implantation for primary prevention in heart failure a high percentage of patients never have appropriate ICD discharges. In addition 25-50 % of CRT patients have no therapeutic effect. Moreover, both ICDs and CRTs are associated with malfunction and complications (e. g. inappropriate shocks, infection). Last but not least is the relatively high cost of these devices. Therefore, it is essential, not only from a clinical but also from a socioeconomic point of view, to optimise the current selection criteria for ICD and CRT. This review focusses on the role of cardiac sympathetic hyperactivity in optimising ICD selection criteria. Cardiac sympathetic hyperactivity is related to fatal arrhythmias and can be non-invasively assessed with ¹²³I-meta-iodobenzylguanide (¹²³I-mIBG) scintigraphy. We conclude that cardiac sympathetic activity assessed with ¹²³I-mIBG scintigraphy is a promising tool to better identify patients who will benefit from ICD implantation.

Keywords: 123I-mIBG scintigraphy; Cardiac resynchronisation therapy; Cardiac sympathetic activity; Heart failure; Implantable cardioverter defibrillator; Prognosis.

Fig. 1

Number of deaths as a result of acute myocardial infarction and heart failure in the Netherlands from 1980 to 2010. The decrease in the number of deaths after myocardial infarction declines more rapidly than the increase in the number of deaths due to heart failure. Source: Centraal Bureau voor de Statistiek (CBS), the Netherlands

Fig. 2

Schematic representation of the sympathetic synapse. Norepinephrine is synthesised 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 synthesised 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 reuptake 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 metabolised in cytosol dihydroxyphenylglycol (DHPG) by monoamine oxidase (MAO)

Fig. 3

Two examples of planar cardiac ¹²³I-mIBG scintigraphy using a medium collimator with different late (4h p.i.) myocardial ¹²³I-mIBG uptake in subjects with the same LVEF compared with a healthy subject. a 63-year-old patient with ischaemic heart failure. b 68-year-old patient with ischaemic heart failure. c 32-year-old healthy person. d Example of placing a region-of-interest (ROI) over the heart (H) and fixed rectangular mediastinal ROI placed on the upper part of the mediastinum (M) for calculating H/M ratio

Fig. 4

Example of late ¹²³I-mIBG SPECT imaging. On the left the conventional short, vertical and horizontal axis, in the middle the corresponding 17-segment model polar map and on the right a 3D reconstruction. There is impaired regional ¹²³I-mIBG uptake in the inferior wall from the myocardial base until the apex with extension to both inferoseptal and inferolateral regions