AbstractBackgroundCardiac resynchronization therapy (CRT) is an established therapy for advanced congestive heart failure, improving both survival and hospitalization. The mechanism beneath these improvements still needs to be defined as about one‐third of the patients do not benefit from resynchronization. Restoration of sympatho‐vagal function can play a significant role in the process, but available data are limited. In this scenario, positron emission tomography scans with 11C‐hydroxyephedrine, a noradrenaline analogous, has the potential to characterize the modifications of the sympathetic nervous system induced by CRT in decompensated patients.Materials and methodsTen patients (six males, age 68 ± 10 years) with primary dilated cardiomyopathy were studied before and after resynchronization (acutely and after 3 months), from a clinical and echocardiographic point of view. Their cardiac sympathetic nerve activity was evaluated by 11C‐hydroxyephedrine positron emission tomography before resynchronization, at short and medium term after resynchronization.ResultsResponders to CRT (patients showing ≥ 15% decrease in left ventricular end‐systolic volume) showed a higher level of left ventricular radiotracer uptake both at baseline and after resynchronization with respect to nonresponders. This was coupled with a progressive improvement in homogeneity in left ventricular tracer uptake mainly in responders.ConclusionsCardiac resynchronization therapy improves cardiac sympathetic nerve activity in responders since its activation, while nonresponders do not show any significant change at any time of evaluation. CRT seems to be more effective in those patients with a still structurally preserved, yet functionally impaired, neuroautonomic system.