ACCELERATED TRACER WASHOUT IN REGIONS OF SYMPATHETIC DENERVATION IN HEART FAILURE PATIENTS WITH ISCHEMIC CARDIOMYOPATHY USING FLUBROBENGUANE POSITRON EMISSION TOMOGRAPHY IMAGING

Abstract

<h3>BACKGROUND</h3> Sympathetic denervation has been shown to predict the risk of sudden cardiac death in ischemic cardiomyopathy (ICM) heart failure patients with implanted cardiac defibrillators. The previous PAREPET trial (JACC 2014;63(2):141) used the PET tracer hydroxyephedrine (HED) which is a false neurotransmitter analog of norepinephrine. This established tracer is labeled with the short-lived isotope C-11, which limits its widespread utility for risk stratification in clinical practice. The purpose of this study was to evaluate the ability of a new F-18-labeled PET tracer LMI-1195 (flubrobenguane) to measure regional denervation (tracer uptake) as well as sympathetic tone (washout rate) in ICM patients with heart failure. <h3>METHODS AND RESULTS</h3> A subset of patients (N=7) in the LMI-1195 vs HED validation trial underwent early (30 min) and late (4 hours) PET-CT imaging following injection of 3 MBq/kg of flubrobenguane. Five subjects were ICM patients and 2 were healthy normal controls. Regional tracer distribution was quantified on the early and late uptake images using the clinical 4DM-PET analysis program (Ann Arbor, MI). Percent washout rate was measured as (early-late) / early uptake (x100%) using a 9-segment model of left ventricle. In normal controls, there was minimal washout over the 4-hour interval between early and late images (4 +/- 4%). Tracer washout was significantly accelerated (P < 0.0001) in both ischemic regions and in remote (perfused) regions in the ICM patients (21 +/- 10% and 17% +/- 9% respectively), suggesting increased sympathetic tone in the whole-LV of these heart failure patients, with regionally higher tone in the ischemic zone. <h3>CONCLUSION</h3> Initial pilot studies evaluating the novel PET tracer [18F]flubrobenguane as a marker of presynaptic neuronal function in humans with and without HF was performed, showing accelerated washout in regions of sympathetic denervation in patients with ischemic cardiomyopathy. If confirmed in larger studies, this would represent a novel and non-invasive method to quantify cardiac sympathetic activity in-vivo. This new imaging method may be helpful in the future to identify cardiac regions associated with elevated arrhythmogenic risk.