Reappearance of cardiac presynaptic sympathetic nerve terminals in the transplanted heart:: Correlation between PET using 11C-hydroxyephedrine and invasively measured norepinephrine release

Previously, sympathetic reinnervation of the transplanted heart has been described using invasive catheterization techniques and noninvasive radionuclide imaging techniques. However, little is known about the agreement between these 2 methods. Thus, correlation between C-11-hydroxyephedrine (HED) PET and invasively measured norepinephrine (NE) release was investigated in transplant recipients in this study. Methods: Using PET and the catecholamine analog HED, 17 patients were studied between 2 mo and 13.6 y after transplantation. Based on results in completely denervated hearts, areas with HED retention >7%/min were defined as reinnervated. Additionally, transcardiac NE release induced by intravenous tyramine (55 mug/kg) was measured by coronary sinus and aortic catheterization within 1 wk of the PET study. NE levels between coronary sinus and aortic root, Delta NECS-AO, were calculated at baseline and after tyramine administration. Differences of more than 3 SD of baseline (> 163 pg/mL) were interpreted as reinnervation. Results: HED retention indicated reinnervation in 10 patients. Maximal HED retention ranged from 4.3%/min to 16.4%/min. Delta NECS-AO 1 min after tyramine administration ranged between -10 pg/mL and 1157 pg/mL, and 8 patients were above the reinnervation threshold. Fisher's exact test demonstrated good agreement between results of PET and Delta NECS-AO measurements (P = 0.002). Maximal HED retention was also significantly correlated with NE release (r = 0.69; P = 0.001), Conclusion: Results of invasively measured NE release and noninvasive C-11-HED PET are well correlated. This study further supports the usefulness of PET as a noninvasive approach for detection of reappearance of catecholamine uptake sites after heart transplantation.