Potential Uses of ¹²³mIBG and Analogous PET Tracers to Guide Use of Cardiac Implantable Electronic Devices in Heart Failure and Associated Arrhythmias

Heart failure has become a worldwide pandemic, with high morbidity and mortality, and also high costs. While better therapies are improving outcomes, many of the treatments are invasive and expensive, particularly cardiac implantable electronic devices (CIEDs). As the effectiveness of many pharmacologic therapies are attributed to their addressing the neurohormonal pathophysiology underlying heart failure, one would expect that using CIEDs based on neurohormonal parameters would provide more effective use of them. An important component of the neurohormonal system is cardiac adrenergic innervation that can be imaged with single photon radiotracers such as iodine-123 metaiodobenzylguanidine (¹²³I-mIBG) and analogous positron emission (PET) tracers such as carbon-11-metahydroxyephedrine (11C-HED). Adrenergic imaging has consistently been shown to effectively risk stratify patients with heart failure with reduced ejection fraction (HFrEF), and it does so independently of, and in many cases better than, customarily used parameters. In addition, adrenergic imaging has been shown to effectively and independently stratify HFrEF patients in terms of the risk of a lethal ventricular arrhythmic event. For therapeutic guidance, while adrenergic imaging is unlikely to influence institution of guidelines directed pharmacologic treatments, there is much evidence of a potential to help guide use of CIEDs such as biventricular pacemakers for cardiac resynchronization therapy (CRT), ventricular assist devices for end-stage HFrEF (LVAD), and implantable cardioverter defibrillators (ICDs). In particular, ¹²³I-mIBG imaging parameters appear to follow a patient’s clinical response to CRT and perhaps could better identify which patients are more likely to benefit. ¹²³I-mIBG imaging parameters, by identifying when pharmacologic therapy is failing, could show earlier in the disease course when LVAD would be beneficial, and then later help determine when or if patients who already have the device have achieved reverse ventricular remodeling sufficient to consider LVAD explantation. Finally, evidence indicates that adrenergic imaging should be able to more effectively guide use of ICDs than current recommendations that are based largely on ejection fraction, with imaging especially able to identify patients who are very unlikely to benefit from this device that has underappreciated morbidities. In addition, with regard to addressing ventricular arrhythmias, there are studies reporting benefits of adrenergic imaging for guidance of invasive electrophysiological therapeutic procedures. Thus, while CIEDs have provided tremendous benefit to people with advanced heart failure, with technologic advances continuously occurring, radionuclide adrenergic imaging shows much promise in more effectively guiding use of these devices.

Keywords: Adrenergic Innervation, Autonomic Nervous System, Cardiac Resynchronization Therapy (CRT), Cardiac Implantable Electronic Device (CIED), Heart Failure, ¹²³I-mIBG, Implantable Cardioverter Defibrillator (ICD), Left Ventricular Assist Device (LVAD), Radionuclide Adrenergic Imaging, Ventricular Arrhythmias.