Age- and sex-dependent changes in sympathetic activity of the left ventricular apex assessed by (18)F-DOPA PET imaging

BACKGROUND: Sexual dimorphism in cardiac sympathetic outflow has recently gained attention in the context of Takotsubo cardiomyopathy. Previous studies suggest that there are sex- and age-dependent differences in peripheral autonomic control, however, data on cardiac-specific sympathetic activation in aged women and men are lacking. METHODS AND RESULTS: Regional quantitative analysis of cardiac fluorine-18 ((18)F)- Dihydroxyphenylalanine (DOPA) uptake was retrospectively performed in 133 patients (69 females, mean age 52.4±17.7 years) referred for assessment of neuroendocrine tumours (NET) by Positron-Emission-Tomography. Cardiac (18)F-DOPA uptake was significantly higher in women as compared to men (1.33±0.21 vs. 1.18±0.24, p<0.001). This sex-difference was most pronounced in the apical region of the left ventricle (LV, 1.30±0.24 in women vs. 1.13±0.25 in men, p<0.001) and in individuals >55 years of age (1.39±0.25 in women vs. 1.09±0.24 in men, p<0.001). Women showed a prominent increase in myocardial (18)F-DOPA uptake with age with the strongest increase seen in the LV apical region (r = 0.34, p = 0.004). Accordingly, sex and age were selected as significant predictors of LV apical (18)F-DOPA uptake in a stepwise linear regression model. No age-dependent changes of cardiac (18)F-DOPA uptake were observed in men or in the right ventricular region. CONCLUSION: Our study suggests that aging is related to sex-specific changes in regional cardiac sympathetic activity. Future studies will have to assess whether the increase in LV apical (18)F-DOPA uptake with age in women is of pathogenic relevance for the higher susceptibility of postmenopausal women to conditions associated with increased sympathetic activity.