Enhanced sympathetic activity as a mechanism of Atrial Fibrillation

We are poor in predicting, which individual patient suffering from atrial fibrillation(AF) benefits from rhythm control strategies. Cardioversion restores sinus rhythm, but does not prevent recurrence of AF. Hence, up to 70% of patients undergoing cardioversion have an arrhythmia recurrence within the year. Antiarrhythmic drugs may be effective predominantly in patients with electrical atrial remodelling (that is: AF induced action potential shortening, down regulation of ion channels or gap junctions). The role of the autonomic nervous system (ANS) in onset and perpetuation of AF remains incompletely understood. There are patients that specifically experience AF during high vagal tone, or, conversely during exercise. Therefore, the ANS plays a role in initiation of AF and in atrial autonomic remodelling in at least some, but probably in many patients. This notion, however, has had modest impact on the clinical care of patients.
Stimulation of the intrinsic cardiac ANS exerts both increased parasympathetic and sympathetic activity, leading to shortening of the atrial and pulmonary vein action potential duration (parasympathetic effect), and increase of intracellular [Ca2+] (sympathetic effect). The increased sympathetic activity observed in patients with AF may well be the result of the ongoing arrhythmia, rather than an independent phenomenon that causes the arrhythmia. In other words, it may be that patients with restoration of sinus rhythm will have a decrease in sympathetic tone, while other patients will remain a high tone. It is relevant to distinct between both causes, because it will heavily affect the targeted clinical strategy to prevent recurrence of AF in these patients.
However, subjecting every patient to invasive testing of the effect of the ANS to assess the patient specific effect is not feasible and exposes patients to potential adverse events. Hence, 123I-mIBG scintigraphy allows non-invasive quantification of the sympathetic activity in the heart.

Patients with new-onset or recurrent AF have an altered myocardial sympathetic activity. The quantification of sympathetic activity with 123I-mIBG scintigraphy, as well as its change over time after restoration of sinus rhythm, can be used to target therapy and predict AF recurrence.

Patients who are in AF and scheduled for an elective cardioversion will undergo 123I-mIBG scintigraphy within 7 days before and six week after the cardioversion. At the same moment, a blood sample (35 ml) will be collected. Patients will be followed for 1 year, with rhythm monitoring by a 24-hours Holter at 6 and 12 months. Furthermore, at these moments another blood sample (35 ml) will be collected. The blood samples will be analysed in collaboration with the "Bioinformatics Laboratory".

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