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.
METHODS AND RESULTS
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.
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
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