123I-mIBG scintigraphy: Yet another risk stratifier for the heart failure toolbox!

Sudden cardiac death (SCD) is the number one killer of adults in industrialized countries, responsible for the death of more than 300,000 Americans annually. This is a staggering number surpassing the total annual number of deaths from all cancers. It is established that malignant ventricular arrhythmias namely ventricular fibrillation constitute the most common mechanism of SCD. Survival of sudden cardiac arrest victims depends primarily on the time to defibrillation and return to a hemodynamically perfusing rhythm. Because of the hurdles hindering prompt defibrillation, survival of sudden cardiac arrest victims to hospital discharge continues to be very poor. Implantable cardioverter-defibrillators (ICD) are devices that are implanted in high risk patients to protect them against SCD. Large randomized trials have demonstrated the benefits of the ICD in reducing total mortality in survivors of sudden cardiac arrests as well as in patients who are at high risk for SCD. Identifying those high risk patients who may benefit from an ICD implantation has been the subject of multiple clinical trials over the past two decades. Indices of electrical instability or alternans and autonomic tone to mention a few have been proposed as markers of high risk substrate with varying degrees of accuracy in predicting clinical events. To date, however, only the measure of left ventricular function as assessed by the ejection fraction (EF) continues to be the clinical tool used to determine eligibility for ICD therapy. Still, most SCD events happen in patients who are not eligible for ICD therapy based on EF. In addition, the lifelong likelihood of appropriate therapy in ICD recipients is very low. These issues with low sensitivity and specificity in our current patient selection criteria for ICD therapy constitute the main impetus behind the search for newer and better risk stratification parameters. I-123 meta-iodobenzylguanidine (mIBG) is a guanethidine-based false neurotransmitter analog of norepinephrine (NE) that is taken by the myocardial sympathetic nerve terminal via the norepinephrine transporter 1 (NET 1). But unlike NE, mIBG is not catabolized after its uptake. Thus, it facilitates imaging of sympathetic nerve terminal function. The avid uptake of mIBG by the myocardium is an indication of intact sympathetic nerve terminal function, whereas the paucity of myocardial uptake measured as a low heart to mediastinal (HM) ratio on planar imaging is an indication of sympathetic dysfunction. It is well established that the heart failure state is characterized by a functional impairment NET 1, and thus poor myocardial uptake of mIBG. Changes in the mIBG HM ratio reflect progression or improvement in heart failure severity. In March 2013, the United States Food and Drug administration approved I-123 mIBG imaging for ‘‘the assessment of myocardial sympathetic innervation in the evaluation of patients with NYHA class II-III heart failure and EF \35%’’. The approval was based primarily on the ADMIRE-HF (AdreView Myocardial Imaging for Heart Failure) study which comprised two North American multicenter phase III studies of a total of 961 patients with NYHA Class II-III heart failure due to ischemic or non-ischemic cardiomyopathy, EF \35% and guideline-recommended optimal medical therapy. Notably, patients with any prior ventricular tachyarrhythmia treated with defibrillation or ICD implantation Reprint requests: Samir Saba, MD, Division of Cardiology, UPMC Presbyterian, University of Pittsburgh Medical Center, 200 Lothrop Street, Suite B 535, Pittsburgh, PA 15213; sabas@upmc.edu J Nucl Cardiol 2014;21:909–12. 1071-3581/$34.00 Copyright 2014 American Society of Nuclear Cardiology.