Treatment of unexplained syncope: a multicenter, randomized trial of cardiac pacing guided by adenosine 5'-triphosphate testing

Background— The origin of 40% of syncope cases remains unknown even after a complete diagnostic workup. Previous studies have suggested that ATP testing has value in selecting successful therapy. This patient-blinded, multicenter, randomized superiority trial tested whether, in patients with syncope of unknown origin, selecting cardiac pacing in those with a positive ATP test leads to fewer recurrences than those who do not receive pacing. Methods and Results— From 2000 to 2005, 80 consenting patients (mean age, 75.9±7.7 years; 81% women; 56% without diagnosed structural heart disease) with syncope of unknown origin and atrioventricular or sinoatrial block lasting >10 seconds (average, 17.9±6.8 seconds) under ATP administration (20-mg IV bolus) were recruited from 10 hospitals, implanted with programmable pacemakers, and randomized to either active pacing (dual-chamber pacing at 70 bpm) or backup pacing (atrial pacing at 30 bpm). Patients were followed up regularly for up to 5 years for any syncope recurrence, the primary outcome. Mean follow-up was 16 months. Syncope recurred in 8 of 39 patients (21%) randomized to active pacing and in 27 of 41 (66%) randomized to backup pacing (control), yielding a hazard ratio of 0.25 (95% confidence interval, 0.12–0.56). After recurrence, the 27 recurrent control patients were reprogrammed to active pacing, and only 1 reported subsequent syncope. Conclusion— This study suggests that, in elderly patients with syncope of unknown origin and positive ATP tests, active dual-chamber pacing reduces syncope recurrence risk by 75% (95% confidence interval, 44–88). Clinical Trial Registration— URL: http://www.controlled-trials.com/ISRCTN00029383 . Unique identifier: ISRCTN00029383.