Abstract 3305: FDG PET Imaging in the PRKAG2 Cardiac Syndrome Demonstrates Altered Myocardial Glucose Uptake
Background : The PRKAG2 gene encodes for the gamma-2 subunit of AMP-activated protein kinase (AMPK), a protein implicated in the regulation of myocardial glucose metabolism. In humans, mutations of the PRKAG2 gene result in a cardiomyopathy characterized by ventricular pre-excitation, atrioventricular conduction disease, and cardiac hypertrophy. It is recognized that altered cardiac glucose metabolism and abnormal glycogen stores are responsible for the clinical manifestations of this syndrome. Since myocardial glucose uptake can be measured with 2-[18F]Fluoro-2-deoxyglucose dynamic positron emission tomography ([18F]FDG PET), we examined whether adult patients with an identified Arg302Gln PRKAG2 mutation have altered myocardial glucose uptake using this imaging modality.
Methods: [18F]FDG PET was performed in 5 adult patients with the Arg302Gln PRKAG2 mutation (PRKAG2) and in 6 healthy volunteers (Control) with a hyperinsulinemic euglycemic clamp protocol. The fractional rate of radiotracer uptake (K) is derived from PATLAK analysis. The rate of myocardial glucose uptake (rMGU) of the left ventricle (LV) is calculated as (K / LC) x Pglucose, where Pglucose represents the mean plasma glucose level during imaging. LC (lump constant) corrects for the differences in the transport and phosphorylation of [18F]FDG and glucose. Results are expressed as mean ± standard deviation and are analyzed with the student t-test.
Results: The mean rMGU in the PRKAG2 group was significantly lower than the control group. There was no difference in the mean plasma glucose levels between the 2 groups. (Table⇓)
Conclusion: Myocardial glucose uptake is reduced in adult patients with mutation of the PRKAG2 gene when compared to normal controls. Measurement of rMGU using [18F]FDG PET imaging appears to be a useful tool to investigate the pathophysiology of the PRKAG2 cardiac syndrome and to potentially distinguish this metabolic cardiomyopathy from other etiolgies.