Cardiac sympathetic hypo-innervation in familial dysautonomia

Objective: Familial dysautonomia (FD) involves incomplete development of the sympathetic nervous system. Whether such loss extends to sympathetic innervation of the heart has been unknown. This study used 6-[ ¹⁸F]fluorodopamine neuroimaging to assess cardiac sympathetic innervation and function in FD. Methods: Six adult FD patients underwent thoracic PET scanning for 30 minutes after i.v. 6-[¹⁸F]fluorodopamine injection, as did healthy volunteers without (N = 21) or with (N = 10) pre-treatment by desipramine, which interferes with neuronal uptake and thereby simulates effects of noradrenergic denervation. Effective rate constants for uptake and loss were calculated using a single compartment pharmacokinetic model. Results: FD patients had decreased uptake and accelerated loss of 6-[¹⁸F]fluorodopamine-derived radioactivity in the interventricular myocardial septum (P = 0.009, P = 0.05) and ventricular free wall (P = 0.007, P < 0.001), compared to untreated controls. Desipramine-treated subjects had decreased uptake but normal loss of 6-[¹⁸F]fluorodopamine-derived radioactivity. Conclusions: FD involves cardiac noradrenergic hypo-innervation. Since accelerated loss of 6-[¹⁸F]fluorodopamine-derived radioactivity cannot be explained by decreased neuronal uptake alone, FD may also involve augmented NE loss from extant terminals.