Extracellular adenosine-5’-triphosphate (ATP) suppresses cardiac pacemakers’ automaticity and AV nodal conduction directly and indirectly by adenosine and a triggered cardio-cardiac vagal reflex. This action constitutes the rationale for the ATP-test, a diagnostic tools aimed to identify patients with syncope of unknown origin (SUO) who could benefit from pacemaker therapy. Two criteria have been used to determine a positive outcome of the ATP test: (i) the duration of ATP-induced cardiac pause (CP) due to AV nodal conduction block or suppressed sinus node, ignoring escape beats, and (ii) the maximal RR interval irrespective of the origin of the QRS complexes (RRmax). The test is deemed positive when CP is >10 sec or RRmax >6 sec Two contrasting conclusions regarding the utility of the test have been reached using these two criteria. The aim of the current post-hoc study, was to explain the discrepancy between the two conclusions.

ATP test consists on an I.V. bolus injection of 20mg of ATP into an antecubital vein. We analyzed data of 33 patients-cohort derived from a multicenter study having incorporated 80 SUO patients (Circulation 2012;125:31-6), in which the ATP-test was positive using the CP duration and negative using the RRmax interval. The 47 remaining patients had both tests positive and were excluded from this analysis.

A dual chamber pacemaker was implanted in all 33 patients: in 14 and 19 patients the pacemaker was programmed for DDD70 bpm and AAI30 bpm (control) pacing modes, respectively. Syncope recurred in only one of the 14 DDD70 patients (7%) during a follow up period of 17.0±8.6 months, but in 10 of the 19 AAI30 patients (53%) during 5.3±5.2 months (p<0.009).

This study shows that ATP-test is a useful diagnostic tool for identifying patients with bradycardic syncope who might benefit from pacing therapy when the CP criterion and not the RRmax criterion- is used to determine the outcome of the test.