Cardiac neuronal imaging with I-123-meta-iodobenzylguanidine in heart failure: implications of endpoint selection and quantitative analysis on clinical decisions

There are a number of radiopharmaceuticals that can be used to investigate autonomic neuronal functions [1].Among these, the norepinephrine analogue meta-iodobenzylguanidine (MIBG) labelled with 123I has been widely used and validated as a marker of adrenergic neuron function [2-4]. The first study addressing the prognostic value of 123I-MIBG imaging in heart failure (HF) was that of Merlet et al. [5] in 90 patients suffering from either ischaemic or idiopathic cardiomyopathy. After publication of this study, more recent studies have indicated that patients with HF and decreased late heart-tomediastinum (H/M) ratio or increased myocardial MIBG washout have a worse prognosis than those with normal quantitative myocardial MIBG parameters [6]. However, MIBG scintigraphy has still to reach widespread clinical application mainly because of the value of other cheaper variables such as left ventricular (LV) ejection fraction and brain natriuretic peptide (BNP) plasma levels. The possibility that the detection of mechanical dyssynchrony by innervation imaging might identify patients who would benefit from resynchronization pacing is another area of research interest [7]. In 2010, the landmark AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study was published [8]. This trial consisted of two identical open-label phase III studies enrolling patients in 96 sites in North America and Europe to provide prospective validation of the prognostic role of quantitation of sympathetic cardiac innervation using MIBG. The primary endpoint was the relationship between late H/Mratio and time-to-occurrence of the first event among a combination of HF progression, potentially life-threatening arrhythmic event, and cardiac death. The authors found that a H/M ratio <1.6 provided prognostic information beyond LV ejection fraction, BNP, and New York Heart Association (NYHA) functional class at the time of enrolment. In a recent article in this journal, Parker et al. [9] present the results of a secondary analysis of the ADMIRE-HF study exploring the association of abnormal MIBG imaging and hospitalization events. The results of this study indicate that the H/M ratio may risk-stratify HF patients for cardiac related hospitalization, especially when used in conjunction with BNP.