Treatment of Unexplained Syncope: A Multicenter, Randomized Trial of Cardiac Pacing Guided by Adenosine 5′-Triphosphate Testing

Study Questions:

Does asystole >10 seconds in response to adenosine 5′-triphosphate (ATP) predict a beneficial response to pacing in patients with syncope of unknown origin (SUO)?


In this multicenter study, 80 patients with SUO (mean age 76 years) and a positive ATP test (>10 seconds of asystole in response to intravenous injection of 20 mg ATP) received a dual-chamber pacemaker. The patients then were randomly assigned in a single-blind fashion to dual-chamber pacing at 70 bpm (active pacing group, n = 39) or atrial pacing at 30 bpm (control group, n = 41). The patients were seen in follow-up every 6 months for up to 5 years. The primary endpoint was recurrence of syncope.


At 2 years of follow-up, the incidence of recurrent syncope was significantly lower in the active pacing group (23%) than in the control group (69%). Overall, active pacing reduced the risk of recurrent syncope by 75%.


A positive ADP test identifies patients with SUO who are likely to respond beneficially to dual-chamber pacing.


ATP exerts a strong vagotonic effect and presumably identified patients in this study with SUO due to vagally-mediated syncope. The number of patients screened for inclusion in this study was not disclosed, but the fact that it took 5 years to identify 80 patients with a positive ATP test at >10 centers suggests that the sensitivity of the ATP test in SUO is low. It also is noteworthy that the study was only single-blinded. Prior single-blind studies demonstrated a beneficial effect of pacing in patients with vagally-mediated syncope, but this was not confirmed in studies that were double-blind.

Clinical Topics: Arrhythmias and Clinical EP, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias

Keywords: Incidence, Recurrence, Follow-Up Studies, Syncope, Vasovagal, Cardiac Pacing, Artificial, Sick Sinus Syndrome, Heart Arrest, Electrocardiography, Single-Blind Method

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